Lack of Association between IFN-γ, CXCL10 and TGF-ß1 Gene Polymorphisms and Liver Complication in HIV-infected Thais.

OBJECTIVE: Chronic liver disease has become a leading cause of illness and death in people living with HIV and the production of the cytokines IFN-γ and TGF-ß1, and chemokine CXCL10 during chronic inflammation contributes to liver disease progression in HIV patients under long-term anti-retroviral therapy. This study aimed to examine association of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-ß1 -509C/T single nucleotide polymorphisms (SNPs) with liver complications in the HIV-infected Thais. METHODS: A cross-sectional study was conducted in 200 Thai HIV patients who were evaluated for transaminitis and significant liver fibrosis by fibrosis-4 score (FIB-4), and genotypes for IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-ß1 -509C/T SNPs using PCR-based methods. RESULT: There were high rates of transaminitis (30.1%) and significant liver fibrosis assessed by FIB-4 score > 1.45 (18.8%) in this group of patients, mostly under anti-retroviral therapy (73.0%). The genotypes and alleles of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-ß1 -509C/T SNPs were not associated with either transaminitis or FIB-4 score > 1.45 (p > 005). Logistic regression analysis identified age and gender as risk factors, and CD4+ cell count higher than 350 cells/ul as a protective factor of liver fibrosis in this study group. CONCLUSION: The IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-ß11 -509C/T SNPs were not significantly associated with liver complication in HIV-infected Thais, mostly under ART.

Genotypic and allelic distribution of IFN-γ +874T/A and TGF-ß1 -509C/T single-nucleotide polymorphisms in human immunodeficiency virus-infected Thais.

Advances in antiretroviral therapy (ART) have led to a decrease of acquired immunodeficiency syndrome (AIDS)-related mortality, and an increase of non-AIDS illnesses in people living with HIV (PLWH). Risks for HIV-related chronic inflammation leading to non-AIDS illnesses in PLWH have been increasingly clarified including immunogenetic factors. This study aimed to examine distribution of genotypic and allelic frequencies of the well-characterized interferon-γ (IFN-γ) +874T/A and transforming growth factor-ß1 (TGF-ß1) -509C/T single nucleotide polymorphisms (SNPs) in Thai PLWH. The cross-sectional study was conducted in 191 Thai HIV patients. Most patients were under ART (74.3%) and maintained a relatively high median of CD4+  cell count (364.5 [5-1601] cells/µl). The frequencies of IFN-γ +874T/A  SNP genotypes were 9.0% AA, 38.3% AT, and 52.7% TT and those of the SNP alleles were 28.1% A and 71.9% T. The rates of TGF-ß1-509C/T SNP genotypes were 15.7% CC, 44.0% CT, and 40.3% TT and those of the SNP alleles were 37.7% C and 62.3% T. The more frequent TT genotypes and T allele of the IFN-γ +874T/A SNP, and relatively more prevalent TT and CT genotypes and T allele of TGF-ß1 -509C/T SNP were potentially associated with disease progression to non-AIDS complication in Thai PLWH and required further investigation. This study provides the immunogenetic data potentially supporting mechanisms for chronic immune activation in PLWH under long-term suppressive ART.

CXCL12 G801A polymorphism is associated with significant liver fibrosis in HIV-infected Thais: a cross-sectional study.

BACKGROUND: Previous studies indicate high prevalence of liver diseases in HIV-infected patients, and their genetic risk factors are still unclear. The chemokine CXCL12 plays important roles in development of chronic liver injury and a single nucleotide polymorphism (SNP) G to A change at position 801 in CXCL12 gene has been demonstrated to affect CXCL12 production levels. OBJECTIVE: This study aimed to analyze the association of CXCL12 G801A SNP with liver complication in HIV-infected Thais. METHODS: A cross-sectional study was conducted in 164 patients who were evaluated for transaminitis and significant liver fibrosis, defined by fibrosis-4 (FIB-4) score and AST to platelet ratio index (APRI), and genotyped for the SNP using tetra-primer PCR-SSP. RESULTS: There were high rates of patients with transaminits (28.0%), and significant liver fibrosis by FIB-4 score (18.9%) and by APRI (14.0%). The CXCL12 G801A AA/GA genotypes were significantly associated with transaminitis (p = 0.014) and significant fibrosis by APRI (p = 0.020). Univariate and multivariate analyses identified the AA/GA genotypes as predictive factors for significant fibrosis (OR 6.8, 95%CI 1.7-28.2, p = 0.008), together with age older than 40 years, CD4+ cell count < 350 cells/µl and hepatitis B and/or C virus coinfection. The significantly higher medians of APRI and FIB-4 score, in patients with AA/GA than those with GG genotypes (p < 0.05) were observed in the ART-naïve, but not ART-experienced groups. CONCLUSION: The CXCL12 G801A AA/GA genotypes are significant predictive factors for hepatic fibrosis potentially in the ART-naïve HIV-infected Thais.