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

Abstract

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.