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Objetivos de este website de Epidemiología Molecular de Enfermedades Infecciosas (EMEI)Este portal de EMEI pretende ser una plataforma de divulgación:

– Científica en el área de la Epidemiología Molecular de Enfermedades Infecciosas aplicada a pacientes infectados por distintos microorganismos que producen infecciones víricas (SIDA, hepatitis C, etc.) ó infecciones bacterianas (sepsis, etc.).

– De las actividades científicas (artículos científicos, comunicaciones a congresos, etc.) realizadas por el grupo de investigación formado en torno a la Unidad de Infección Viral e Inmunidad del Centro Nacional de Microbiología (Instituto de Salud Carlos III, Majadahoda, Madrid), cuyo responsable es el Dr. Salvador Resino García

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EMEI- Últimos artículos científicos publicados:

  • Single nucleotide polymorphisms of CXCL9-11 chemokines are associated with liver fibrosis in HIV/HCV-coinfected patients. -

    Single nucleotide polymorphisms of CXCL9-11 chemokines are associated with liver fibrosis in HIV/HCV-coinfected patients.

    J Acquir Immune Defic Syndr. 2014 Dec 31;

    Authors: Pineda-Tenor D, Berenguer J, García-Álvarez M, Guzmán-Fulgencio M, Carrero A, Aldámiz-Echevarria T, Tejerina F, Diez C, Jiménez-Sousa MA, Fernández-Rodríguez A, Ángeles Munoz-Fernandez M, Resino S

    Abstract
    BACKGROUND:: CXCR3A-associated chemokines (CXCL9-11) are implicated in the pathogenesis of hepatitis C virus (HCV) infection. We analyzed the association between CXCL9-11 polymorphisms and significant liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients.
    METHODS:: We performed a cross-sectional study in 220 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using GoldenGate® assay. Three outcome variables related to liver fibrosis were studied: a) F≥2; b) APRI≥2; and c) FIB-4≥3.25.
    RESULTS:: The percentage of patients with significant liver fibrosis (F≥2, APRI≥2, and FIB-4≥3.25) was significantly higher for CXCL9 rs10336 TT (p=0.046, p=0.010, and p=0.046; respectively), CXCL10 rs3921 GG (p=0.046, p=0.011, and p=0.049; respectively), and CXCL11 rs4619915 AA (p=0.035, p=0.014, and p=0.057; respectively) genotypes. Moreover, the greater likelihood of having significant liver fibrosis (F≥2, APRI≥2, and FIB-4≥3.25) was found in carriers of CXCL9 rs10336 TT and CXCL10 rs3921 GG (adjusted odds ratio (aOR)>2 (p<0.05)). These trends were significantly more pronounced in patients infected with HCV-genotype 1 (GT1) (aOR>3 (p<0.05)). Moreover, TGA haplotype showed higher odds for having values of APRI≥2 (aOR=2.4; p=0.012) when we considered all patients. This elevated risk for significant liver fibrosis was better represented in patients infected with HCV-GT1, where TGA haplotype had increased odds for having values of F≥2 (aOR=1.9; p=0.045), APRI≥2 (aOR=3.2; p=0.009) and FIB-4≥3.25 (aOR=3.3; p=0.026).
    CONCLUSIONS:: The homozygosity for the minor alleles CXCL9 rs10336 (T), CXCL10 rs3921 (G) and CXCL11 rs4619915 (A) is associated with the higher likelihood of significant liver fibrosis in HIV infected patients coinfected with HCV-GT1.

    PMID: 25559603 [PubMed - as supplied by publisher]

  • Transcriptomic correlates of organ failure extent in sepsis. -

    Transcriptomic correlates of organ failure extent in sepsis.

    J Infect. 2014 Dec 31;

    Authors: Almansa R, Heredia Rodríguez M, Gomez-Sanchez E, Andaluz-Ojeda D, Iglesias Mlt V, Rico Mlt L, Ortega Mlt A, Gomez-Pesquera E, Liu P, Aragón M, Eiros JM, Jiménez-Sousa MÁ, Resino S, Gómez-Herreras I, Bermejo-Martín JF, Tamayo E

    Abstract
    OBJECTIVES: Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients.
    METHODS: Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score.
    RESULTS: The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality.
    CONCLUSIONS: The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.

    PMID: 25557485 [PubMed - as supplied by publisher]

  • FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients. -
    Related Articles

    FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.

    BMC Med. 2014;12:198

    Authors: Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, García-Alvarez M, Aldámiz-Echevarria T, Carrero A, Vázquez-Morón S, García-Broncano P, Diez C, Tejerina F, Guzmán-Fulgencio M, Resino S

    Abstract
    BACKGROUND: The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients.
    METHODS: We carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFNα/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ≥2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR).
    RESULTS: The rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ≥27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ≥2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%.
    CONCLUSIONS: Patients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.

    PMID: 25367448 [PubMed - in process]

  • rs7903146 Polymorphism at Transcription Factor 7 Like 2 Gene Is Associated with Total Cholesterol and Lipoprotein Profile in HIV/Hepatitis C Virus-Coinfected Patients. -
    Related Articles

    rs7903146 Polymorphism at Transcription Factor 7 Like 2 Gene Is Associated with Total Cholesterol and Lipoprotein Profile in HIV/Hepatitis C Virus-Coinfected Patients.

    AIDS Res Hum Retroviruses. 2014 Oct 29;

    Authors: Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, Carrero A, García-Álvarez M, Aldámiz-Echevarria T, García-Broncano P, Diez C, Guzmán-Fulgencio M, Fernández-Rodríguez A, Resino S

    Abstract
    Abstract Transcription factor 7 like 2 (TCF7L2) rs7903146 polymorphism has been associated with metabolic disturbance and cardiovascular disease. The aim of this study was to analyze the association between TCF7L2 rs7903146 polymorphism and potential disturbances on the lipid profile in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We performed a cross-sectional study on 263 HIV/HVC-coinfected patients. TCF7L2 polymorphism was genotyped by GoldenGate assay. The analysis was performed by linear and logistic regression under a dominant model of inheritance. The variables analyzed were total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), non-HDL-C, and triglycerides. Patients harboring the rs7903146 TT/TC genotype showed a diminished concentration of TC (p=0.003), LDL-C (p=0.004), HDL-C (p=0.012), and non-HDL-C (p=0.013), a lower percentage of TC≥200 mg/dl (p=0.038), and a higher percentage of HDL≤40 mg/dl (p=0.023). In addition, we observed that rs7903146 was differently related to fasting serum lipid levels according to the HCV-genotype (HCV-GT). With regard to HCV-GT1 patients, the rs7903146 TT/TC genotype was associated with lower levels of HDL-C [adjusted arithmetic mean ratio (aAMR)=0.91; p=0.049] and an elevated percentage of patients with HDL-C≤40 mg/dl [adjusted odds ratio (aOR)=3.26; p=0.003]. For HCV-GT3 patients, the rs7903146 TT/TC genotype was associated with lower serum values of TC (aAMR=0.81; p=0.037), LDL-C (aAMR=0.67; p=0.001), and non-HDL-C (aAMR=0.75; p=0.002) and a reduced percentage of TC≥200 mg/dl (aOR=0.089; p=0.037). In conclusion, the TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of TC, LDL, and HDL in HCV-GT3 patients, and lower levels of HDL-C in HCV-GT1 patients, suggesting a role in cardiovascular disease and a potential use as a biomarker in HIV/HCV-coinfected patients.

    PMID: 25353718 [PubMed - as supplied by publisher]

  • Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients. -
    Related Articles

    Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.

    Eur J Clin Microbiol Infect Dis. 2014 Sep 19;

    Authors: Guzmán-Fulgencio M, Berenguer J, Pineda-Tenor D, Jiménez-Sousa MA, García-Álvarez M, Aldámiz-Echevarria T, Carrero A, Diez C, Tejerina F, Vázquez S, Briz V, Resino S

    Abstract
    Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

    PMID: 25236396 [PubMed - as supplied by publisher]

  • CXCL9, CXCL10 and CXCL11 polymorphisms are associated with sustained virologic response in HIV/HCV-coinfected patients. -
    Related Articles

    CXCL9, CXCL10 and CXCL11 polymorphisms are associated with sustained virologic response in HIV/HCV-coinfected patients.

    J Clin Virol. 2014 Nov;61(3):423-9

    Authors: Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, Guzmán-Fulgencio M, Aldámiz-Echevarria T, Carrero A, García-Álvarez M, Diez C, Tejerina F, Briz V, Resino S

    Abstract
    BACKGROUND: The CXCL9, CXCL10 and CXCL11 (CXCL9-11) chemokines play a critical role in eradication of hepatitis C virus (HCV), although HCV-specific immunity often fails to eradicate the HCV, allowing the chronicity of hepatitis C.
    OBJECTIVE: To examine the association between CXCL9-11 polymorphisms and the sustained virological response (SVR) following hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin in HIV/HCV-coinfected patients.
    STUDY DESIGN: We performed a retrospective study in 176 naïve patients who started HCV treatment. The CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 polymorphisms were genotyped by GoldenGate(®) assay. Genetic data were analyzed under recessive inheritance model. The SVR was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment.
    RESULTS: In the intention-to-treat analysis, the SVR rate was higher in HCV genotype 1/4 (GT1/4) patients carrying rs10336 TT (p=0.042), rs3921 GG (p=0.021), and rs4619915 AA (p=0.024) genotypes; and they had higher likelihood of achieving SVR (adjusted odds ratio (aOR)=3.26 (p=0.038), aOR=4.21 (p=0.019), and aOR=4.08 (p=0.022), respectively). For CXCL haplotype analysis (CXCL9/rs10336, CXCL10/rs3921, and CXCL11/rs4619915), the TGA haplotype (favorable alleles) had better odds of achieving SVR than the CCG haplotype (unfavorable alleles) in GT1/4patients (OR=2.69; p=0.003). No significant results were found in GT2/3 patients. Moreover, similar results were obtained in the on-treatment analysis.
    CONCLUSIONS: The presence of homozygous for the minor allele of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 was related to higher likelihoods of achieving the HCV clearance after pegIFNα/ribavirin therapy in HIV infected patients coinfected with HCV GT1/4.

    PMID: 25218243 [PubMed - in process]

  • Relationship between European mitochondrial haplogroups and chronic renal allograft rejection in patients with kidney transplant. -
    Related Articles

    Relationship between European mitochondrial haplogroups and chronic renal allograft rejection in patients with kidney transplant.

    Int J Med Sci. 2014;11(11):1129-32

    Authors: Jiménez-Sousa MA, Tamayo E, Guzmán-Fulgencio M, Fernández-Rodríguez A, Heredia-Rodriguez M, García-Álvarez M, Bermejo-Martin JF, Pineda-Tenor D, Ruiz-Granado P, Alvarez-Fuente E, Gómez-Sanchez E, Gómez-Herreras JI, Resino S

    Abstract
    Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom's MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction.

    PMID: 25170295 [PubMed - in process]

  • PPARγ2 Pro12Ala polymorphism was associated with favorable cardiometabolic risk profile in HIV/HCV coinfected patients: a cross-sectional study. -
    Related Articles

    PPARγ2 Pro12Ala polymorphism was associated with favorable cardiometabolic risk profile in HIV/HCV coinfected patients: a cross-sectional study.

    J Transl Med. 2014;12:235

    Authors: García-Broncano P, Berenguer J, Fernández-Rodríguez A, Pineda-Tenor D, Jiménez-Sousa MÁ, García-Alvarez M, Miralles P, Aldámiz-Echevarria T, López JC, Micheloud D, Resino S

    Abstract
    BACKGROUND: Peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2) rs1801282 (Pro12Ala) polymorphism has been associated with lower risk of metabolic disturbance and atherosclerosis. The aim of this study was to analyze the association between the Pro12Ala polymorphism and cardiometabolic risk factors in human immunodeficiency virus (HIV)/Hepatitis C virus (HCV)-coinfected patients.
    METHODS: We carried out a cross-sectional study on 257 HIV/HCV coinfected patients. PPARγ2 polymorphism was genotyped by GoldenGate® assay. The main outcome measures were: i) serum lipids (cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, and atherogenic index (AI)); ii) homeostatic model assessment (HOMA-IR) values; iii) serum adipokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1(PAI-1), hepatic growth factor (HGF), and nerve growth factor (NGF)). Generalized Linear Models (GLM) with gamma distribution (log-link) were used to investigate the association between PPARγ2 polymorphism and continuous outcome variables. This test gives the differences between groups and the arithmetic mean ratio (AMR) in continuous outcome variables between groups.
    RESULTS: The rs1801282 CG/GG genotype was associated with low values of cholesterol (adjusted arithmetic mean ratio (aAMR) = 0.87 (95% of confidence interval (95% CI) = 0.79; 0.96); p = 0.004) and LDL-C (aAMR = 0.79 (95% CI = 0.68; 0.93); p = 0.004). Furthermore, rs1801282 CG/GG was associated with low values of HOMA-IR (aAMR = 0.69 (95% CI = 0.49; 0.98); p = 0.038) among patients with significant liver fibrosis (F ≥ 2). Moreover, rs1801282 CG/GG was also associated with low serum values of hepatic growth factor (HGF) (aAMR = 0.61 (95% CI = 0.39; 0.94); p = 0.028), and nerve growth factor (NGF) (aAMR = 0.47 (95% CI = 0.26; 0.84); p = 0.010). The serum levels of leptin, adiponectin, resistin, and PAI-1 did not show significant differences.
    CONCLUSIONS: The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with a protective cardiometabolic risk profile versus CC genotype in HIV/HCV-coinfected patients. Thus, PPARγ2 rs1801282 polymorphism may play a significant role in the development of metabolic disorders in HIV/HCV coinfected patients, and might have an influence on the cardiovascular risk.

    PMID: 25159899 [PubMed - in process]

  • Mortality of patients infected with HIV in the intensive care unit (2005-2010): significant role of chronic hepatitis C and severe sepsis. -
    Related Articles

    Mortality of patients infected with HIV in the intensive care unit (2005-2010): significant role of chronic hepatitis C and severe sepsis.

    Crit Care. 2014 Aug 27;18(4):475

    Authors: Medrano J, Alvaro-Meca A, Boyer A, Jiménez-Sousa MA, Resino S

    Abstract
    IntroductionThe combination antiretroviral therapy (cART) has led to decreased opportunistic infections and hospital admissions in human immunodeficiency virus (HIV) infected patients; but the intensive care unit (ICU) admission rate remains constant (or even increased in some instances) during the cART era. Hepatitis C virus (HCV) infection is associated with an increased risk for hospital admission and/or mortality (particularly those related to severe liver disease) compared to the general population. The aim of this study was to assess the mortality among HIV-infected patients in ICU, and to evaluate the impact of HIV/HCV coinfection and severe sepsis on ICU mortality.MethodsWe carried out a retrospective study based on patients admitted to ICU who were recorded in the Minimum Basic Data Set (2005-2010) in Spain. HIV-infected patients (All-HIV-group (n¿=¿1891)) were divided into two groups: HIV-monoinfected patients (HIV-group (n¿=¿1191)) and HIV/HCV-coinfected patients (HIV/HCV-group (n¿=¿700)). A control group (HIV(-)/HCV(-)) was also included (n¿=¿7496).ResultsAll-HIV-group had higher frequencies of severe sepsis (57.7% vs. 39.4%; p¿<¿0.001) than control group. Overall, ICU mortality in patients with severe sepsis was much more frequent than in patients without severe sepsis (other causes) at days 30 and 90 in HIV-infected patients and control group (p¿<¿0.001). Moreover, all-HIV-group in presence or absence of severe sepsis had a higher percentage of death than control group at days 7 (p¿<¿0.001), 30 (p¿<¿0.001) and 90 (p¿<¿0.001). Besides, HIV/HCV-group had a higher percentage of death both in patients with severe sepsis, and in patients without severe sepsis compared to HIV-group at days 7 (p¿<¿0.001) and 30 (p¿<¿0.001); while no differences were found at day 90. In a Bayesian competing risk model, HIV/HCV-group had higher mortality risk (adjusted hazard ratio (aHR)¿=¿1.44 (95%CI¿=¿1.30-1.59) and aHR¿=¿1.57 (95%CI¿=¿1.38-1.78) for patients with and without severe sepsis, respectively).ConclusionsHIV infection was related to higher frequency of severe sepsis and death among patients admitted to the ICU. Besides, HIV/HCV coinfection contributed to an increased risk of death in both presence and absence of severe sepsis.

    PMID: 25159592 [PubMed - as supplied by publisher]

  • PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV-coinfected patients under HCV therapy. -
    Related Articles

    PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV-coinfected patients under HCV therapy.

    J Acquir Immune Defic Syndr. 2014 Oct 1;67(2):113-9

    Authors: Fernández-Rodríguez A, Berenguer J, Rallón N, Jiménez-Sousa MA, López JC, Soriano V, García-Álvarez M, Cosín J, Martínez P, Guzmán-Fulgencio M, Miralles P, Miguel Benito J, Resino S

    Abstract
    OBJECTIVES: To analyze whether peroxisome proliferator-activated receptor gamma (PPARγ2) rs1801282 (Pro12Ala) polymorphism is associated with the response to pegylated-interferon-alpha plus ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients, and whether it is able to predict the outcome of HCV treatment.
    DESIGN: Retrospective follow-up study.
    METHODS: Two hundred eighty-five naive patients, who started HCV-treatment, were genotyped for PPARγ2 and interleukin 28B polymorphisms. Genetic data were analyzed under dominant inheritance model. Sustained virological response (SVR) was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment.
    RESULTS: The variables significantly associated with SVR in a multivariate analysis were HCV-genotype (GT) 3 {adjusted odds ratio [aOR] = 7.66 [95% of confidence interval (95% CI): 3.96 to 14.81] P < 0.001}, HCV-viremia <500,000 IU/mL [aOR = 2.20 (95% CI: 1.16 to 4.15] P = 0.015), no/mild liver fibrosis (F < 2) [aOR = 1.92 (95% CI: 1.08 to 3.42) P = 0.026], IL28B rs12980275 AA genotype [aOR = 2.70 (95% CI: 1.54 to 4.71) P < 0.001], and PPARγ2 rs1801282 CG/GG genotype [aOR = 2.93 (95% CI: 1.27 to 6.72) P = 0.011]. When PPARγ2 rs1801282 genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly classified was 71.6% and the area under the receiver operating characteristic curves was 0.766 ± 0.028.
    CONCLUSIONS: The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with increased odds for achieving SVR in HIV/HCV-coinfected patients on HCV treatment.

    PMID: 25072612 [PubMed - indexed for MEDLINE]

  • Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery. -
    Related Articles

    Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery.

    J Infect. 2015 Jan;70(1):20-9

    Authors: Jiménez-Sousa MA, Tamayo E, Guzmán-Fulgencio M, Heredia M, Fernández-Rodríguez A, Gómez E, Almansa R, Gómez-Herreras JI, García-Álvarez M, Gutiérrez-Junco S, Bermejo-Martin JF, Resino S, Spanish Sepsis Group (SpSG)

    Abstract
    OBJECTIVE: To analyse whether mitochondrial DNA (mtDNA) haplogroups are associated with severe sepsis and mortality after major surgery.
    METHODS: We performed a case-control study on 240 cardiac or abdominal surgery patients developing severe sepsis (Case-group) and 267 cardiac or abdominal surgery patients without severe sepsis and with systemic inflammatory response syndrome (SIRS, Control-group). Furthermore, a longitudinal substudy was performed for analysing the survival in septic patients. Only European white patients within the N macro-cluster were included.
    RESULTS: Case-group underwent cardiac surgery had lower frequencies of cluster HV (p = 0.005) and haplogroup H (p = 0.005) and higher frequencies of cluster JT (p = 0.028) than Control-group; but no significant differences were found for abdominal surgery. Besides, both cluster HV and haplogroup H were associated with decreased odds of severe sepsis (adjusted odds ratio (aOR) = 0.45 (95%CI = 0.25; 0.82); p = 0.009 and aOR = 0.48 (95%CI = 0.26; 0.87); p = 0.015, respectively) among patients underwent cardiac surgery. In Case-group, 45.4% (109/240) patients died with a survival median of 39 (95%CI = 31.4; 46.62) days. When the clusters were examined, 41% (55/134) patients within cluster HV died versus 71.4% (10/14) patients within cluster IWX (p = 0.018). Additionally, patients within cluster IWX had an increased risk of death (adjusted hazard ratio (aHR) = 2.22; (95%CI = 1.14; 4.34); p = 0.019).
    CONCLUSIONS: European mitochondrial haplogroups might be related to the onset of severe sepsis in patients who underwent major cardiac surgery, but not in patients underwent major abdominal surgery. Besides, mtDNA haplogroups could have influence on mortality in septic patients.

    PMID: 25043396 [PubMed - in process]

  • Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: a meta-analysis. -
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    Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: a meta-analysis.

    Hepatology. 2014 Nov;60(5):1541-50

    Authors: García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, Resino S

    Abstract
    UNLABELLED: There is growing evidence that vitamin D is related to chronic hepatitis C (CHC) pathogenicity. We analyzed the relationship of vitamin D status with advanced liver fibrosis (ALF) in CHC treatment-naïve patients and sustained virologic response (SVR) in CHC patients on pegylated interferon alpha plus ribavirin (pegIFNα/ribavirin) therapy. We performed a meta-analysis of all eligible studies published to date (April, 2014) in PubMed, SCOPUS, LILACS, and the Cochrane Library, assessing plasma/serum vitamin D levels related to ALF and/or SVR. Pooled odds ratios (ORs) were estimated by either fixed or random effects models. Fourteen studies were selected from the literature search, seven for ALF (1,083 patients) and 11 for SVR (2,672 patients). For liver fibrosis, low vitamin D status was related to a diagnosis of ALF, with the cutoffs of 10 ng/mL (OR=2.37, 95% confidence interval [CI]=1.20, 4.72) and 30 ng/mL (OR=2.22, 95% CI=1.24, 3.97) being significant, and a near-significance for 20 ng/mL (OR=1.44, 95% CI=0.99, 2.12). Regarding SVR, a significant heterogeneity among studies was found (P<0.001), and we only found a significant association with SVR for a vitamin D cutoff of 20 ng/mL (OR=0.53, 95% CI=0.31, 0.91). When meta-analysis was performed excluding the outliers, significant pooled ORs were found for all patients (10 ng/mL [OR=0.48, 95% CI=0.34, 0.67] and 20 ng/mL [OR=0.58, 95% CI=0.45, 0.76]) and GT1/4 patients (10 ng/mL [OR=0.53, 95% CI=0.34, 0.81] and 20 ng/mL [OR=0.54, 95% CI=0.39, 0.74]).
    CONCLUSION: Low vitamin D status in CHC patients is associated with a higher likelihood of having ALF and lower odds of achieving SVR following pegIFNα/ribavirin therapy.

    PMID: 24975775 [PubMed - indexed for MEDLINE]

  • European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients. -
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    European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients.

    HIV Med. 2014 Aug;15(7):425-30

    Authors: Guzmán-Fulgencio M, Rallón N, Berenguer J, Fernández-Rodríguez A, Soriano V, Miralles P, Jiménez-Sousa MA, Restrepo C, López JC, García-Álvarez M, Aldámiz T, Benito JM, Resino S

    Abstract
    OBJECTIVES: Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV).
    METHODS: We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data.
    RESULTS: The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype.
    CONCLUSIONS: European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.

    PMID: 24580757 [PubMed - in process]

  • Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV-coinfected patients. -
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    Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV-coinfected patients.

    Eur J Clin Invest. 2014 May;44(5):453-62

    Authors: Pineda-Tenor D, Berenguer J, García-Broncano P, Jiménez-Sousa MA, Fernández-Rodríguez A, Diez C, García-Álvarez M, Carrero A, Catalán P, Aldámiz-Echevarria T, Resino S

    Abstract
    BACKGROUND: The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients.
    METHODS: We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC≥200 mg/dL, TG≥170 mg/dL, LDL-C≥100 mg/dL, HDL-C≤35 mg/dL, non-HDL-C≥120 mg/dL and HOMA≥3·8) according to ADIPOQ genotype under a dominant inheritance model.
    RESULTS: Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P=0·038) and percentages of TC≥200 mg/dL (P=0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR)=0·92 [(95% CI=0·85; 0·99) P=0·024]) and low likelihood of TC≥200 mg/dL (odds ratio (OR)=0·32 [(95% CI=0·11; 0·88) P=0·027]. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR=0·89; P=0·027), LDL-C (AMR=0·85; P=0·039) and non-HDL-C (AMR=0·86; P=0·015). No significant associations were found between rs2241766 and HOMA values.
    CONCLUSIONS: The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV-coinfected patients with steatosis.

    PMID: 24528335 [PubMed - indexed for MEDLINE]

  • SLC30A8 rs13266634 polymorphism is related to a favorable cardiometabolic lipid profile in HIV/hepatitis C virus-coinfected patients. -
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    SLC30A8 rs13266634 polymorphism is related to a favorable cardiometabolic lipid profile in HIV/hepatitis C virus-coinfected patients.

    AIDS. 2014 Jun 1;28(9):1325-32

    Authors: Pineda-Tenor D, Micheloud D, Berenguer J, Jiménez-Sousa MA, Fernández-Rodríguez A, García-Broncano P, Guzmán-Fulgencio M, Diez C, Bellón JM, Carrero A, Aldámiz-Echevarria T, García-Álvarez M, Resino S

    Abstract
    OBJECTIVE: To analyze the relationship of SLC30A8 rs13266634 polymorphism with insulin resistance and dyslipidemia in HIV/hepatitis C virus (HCV)-coinfected patients.
    DESIGN: Cross-sectional study in 260 HIV/HVC-coinfected patients.
    METHODS: SLC30A8 polymorphisms were genotyped by GoldenGate assay. Genetic data were analyzed under the dominant inheritance model (CT/TT versus CC). Cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, atherogenic index, and homeostatic model assessment of insulin resistance (HOMA-IR) values were assayed for each genotype.
    RESULTS: rs13266634 CT/TT carriers had higher serum values of HDL-C (P = 0.014) and lower values of LDL-C/HDL-C (P = 0.036) and atherogenic index (P = 0.011) than CC carriers. Additionally, rs13266634 CT/TT carriers had lower percentage of HDL 35 mg/dl or less (P = 0.050) and higher percentage of LDL/HDL at least 3 (P = 0.091) and atherogenic index at least 3.5 (P = 0.003) than CC carriers. When adjusted regression analysis was performed, rs13266634 CT/TT genotype was associated with high serum values of HDL-C [arithmetic mean ratio (AMR) = 1.10 (95% confidence interval, CI = 1.03-1.19) P = 0.006], and low values of LDL-C/HDL-C [AMR = 0.88 (95% CI = 0.79-0.99) P = 0.045] and atherogenic index [AMR = 0.89 (95% CI = 0.81-0.98) P = 0.024]. For categorical outcomes, rs13266634 CT/TT carriers had lower significant likelihood of having atherogenic index at least 3.5 [odds ratio = 0.47 (95% CI = 0.26-0.83) P = 0.009], and very close to significance for LDL-C/HDL-C at least 3 [odds ratio = 0.52 (95% CI = 0.27-1.02) P = 0.056], supporting the protective effect of the CT/TT genotypes. No significant relationship was observed between rs13266634 and HOMA-IR values.
    CONCLUSION: rs13266634 CT/TT genotype was associated to higher levels of HDL-C and lower values of cardiovascular risk indices (LDL-C/HDL-C and atherogenic index), but there was a lack of association with HOMA-IR values. Thus, rs13266634 polymorphism might play a significant role in lipid metabolism and cardiovascular risk in HIV/HCV-coinfected patients.

    PMID: 24499956 [PubMed - in process]