Graduate Program in Medical Technology.
Bureau of AIDS, TB and STIs, Department of Disease Control, Ministry of Public Health, Tiwanon Road, Muang District, Nonthaburi, Thailand.
Asian Pac J Allergy Immunol. 2019 Sep;37(3):162-170. doi: 10.12932/AP-160917-0162.
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.
This study aimed to analyze the association of CXCL12 G801A SNP with liver complication in HIV-infected Thais.
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.
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.
The CXCL12 G801A AA/GA genotypes are significant predictive factors for hepatic fibrosis potentially in the ART-naïve HIV-infected Thais.
先前的研究表明,HIV 感染者中肝脏疾病的患病率较高,但其遗传危险因素尚不清楚。趋化因子 CXCL12 在慢性肝损伤的发展中起着重要作用,并且已经证明 CXCL12 基因中位置 801 的单核苷酸多态性 (SNP) G 到 A 变化会影响 CXCL12 的产生水平。
本研究旨在分析 HIV 感染者泰国人群中 CXCL12 G801A SNP 与肝脏并发症的关系。
对 164 例患者进行了横断面研究,评估了这些患者的肝转氨酶升高和显著肝纤维化,通过纤维化-4 (FIB-4) 评分和天冬氨酸转氨酶与血小板比值指数 (APRI) 来定义,并用四引物 PCR-SSP 对 SNP 进行基因分型。
有很高比例的患者出现肝转氨酶升高 (28.0%),以及通过 FIB-4 评分 (18.9%) 和 APRI (14.0%) 确定的显著肝纤维化。CXCL12 G801A AA/GA 基因型与肝转氨酶升高 (p = 0.014) 和 APRI 确定的显著纤维化显著相关 (p = 0.020)。单因素和多因素分析均确定 AA/GA 基因型是显著纤维化的预测因子 (OR 6.8,95%CI 1.7-28.2,p = 0.008),与年龄大于 40 岁、CD4+ 细胞计数 < 350 个/μl 以及乙型肝炎和/或丙型肝炎病毒合并感染有关。在未接受 ART 治疗的患者中,与 GG 基因型相比,AA/GA 基因型患者的 APRI 和 FIB-4 评分中位数显著更高 (p < 0.05),但在接受 ART 治疗的患者中则没有观察到这种情况。
在未接受 ART 治疗的 HIV 感染泰国人群中,CXCL12 G801A AA/GA 基因型是肝纤维化的重要预测因子。