Association between TGFβ1 polymorphisms and chronic hepatitis B infection in an Iranian population

Abstract INTRODUCTION: Transforming growth factor-beta 1 (TGFβ1) is a potent suppressive cytokine that contributes to chronic hepatitis B (CHB) infection. Disparities in TGFβ1 production among individuals have been attributed to TGFβ1 genetic polymorphisms. We examined whether three putative polymorphisms in TGFβ1[-509 C/T (rs1800469), +869 C/T (rs1800470), and +11929 C/T (rs1800472)]are associated with CHB infection in a South-Eastern Iranian population. METHODS: In total, 341 subjects were recruited, including 178 patients with CHB and 163 healthy individuals as controls. Genotyping of the three TGFβ1 SNPs was performed by tetra amplification refractory mutation system-PCR. RESULTS: TheTGFβ1 +869 TT vs.CC genotype in codominant (OR=0.445, p=0.012) and TT vs. TC+CC in the recessive (OR=0.439, p=0.003) model as well as the variant allele T vs. C(OR=0.714, p=0.038) were associated with lower CHB infection risk. However, the +11929 C/T polymorphism was associated with increased CHB risk, and the CT vs. CC genotype (OR=2.77, P=0.001) and T variant allele (OR=2.53, P=0.002) were risk factors for CHB. Furthermore, TTT (+869/-509/+11929) and CCC haplotypes were risk and protective factors for CHB, respectively. We found no significant association between viral DNA load and TGFβ1 genotype or hepatic enzyme levels (p >0.05). CONCLUSIONS: Results indicated that the TGFβ1+869TT genotype and T allele were protective factors, whereas the +11929 CT genotype and T allele were risk factors for CHB infection.

摘要 引言：转化生长因子-β1（Transforming growth factor-beta 1, TGFβ1）是一种强效抑制性细胞因子，参与慢性乙型肝炎（chronic hepatitis B, CHB）的感染进程。个体间TGFβ1表达水平的差异被认为与TGFβ1基因多态性相关。本研究旨在探讨TGFβ1基因的三个推定多态位点[-509 C/T (rs1800469)、+869 C/T (rs1800470)以及+11929 C/T (rs1800472)]与伊朗东南部人群慢性乙型肝炎感染的相关性。
方法：本研究共招募341名受试者，其中178名慢性乙型肝炎患者为病例组，163名健康个体作为对照组。采用四引物扩增受阻突变体系-聚合酶链反应（tetra amplification refractory mutation system-PCR）对三个TGFβ1单核苷酸多态性位点进行基因分型。
结果：在共显性模型中，TGFβ1 +869 TT基因型相较于CC基因型（比值比OR=0.445，p=0.012），以及隐性模型中TT基因型相较于TC+CC基因型（OR=0.439，p=0.003），还有变异等位基因T相较于C（OR=0.714，p=0.038），均与慢性乙型肝炎感染风险降低显著相关。然而，+11929 C/T基因多态性则与慢性乙型肝炎感染风险升高相关：CT相较于CC基因型（OR=2.77，P=0.001）以及T变异等位基因（OR=2.53，P=0.002）均为慢性乙型肝炎的危险因素。此外，TTT（+869/-509/+11929）与CCC单倍型分别为慢性乙型肝炎的危险因素与保护因素。本研究未发现病毒DNA载量与TGFβ1基因型或肝酶水平存在显著关联（p>0.05）。
结论：本研究结果表明，TGFβ1 +869 TT基因型及T等位基因为慢性乙型肝炎感染的保护因素，而+11929 CT基因型及T等位基因为慢性乙型肝炎感染的危险因素。