慢性乙型肝炎转化生长因子β1基因单核苷酸多态性及单倍型分析

Single nucleotide polymorphisms and haplotype analysis of the transforming growth factor-βl gene in patients with chronic hepatitis B

目的探讨转化生长因子β1（TGF-β1）基因单核苷酸多态性（SNP）及其单倍型与慢性乙型肝炎易感性之间的关系。方法以155例慢性乙型肝炎患者和170例健康对照者为研究对象，应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）和DNA测序的方法对TGF-β1基因-509C／T、869T／C（Leu10Pro）单核苷酸多态性进行基因分型，同时采用酶联免疫吸附试验（ELISA）检测血清TGF-β1水平。用SHEsis软件分析TGF-β1基因的连锁不平衡及单倍型频率。结果TGF-β1基因869T／C（Leu10Pro）多态性在慢性乙型肝炎组和正常人群中的分布差异无统计学意义（P〉0．05），而TGF-β1基因-509C／T多态性在两组人群中的分布差异有统计学意义（P〈0．05），等位基因频率的相对风险分析发现，T等位基因携带者患慢性乙型肝炎的风险是C等位基因的1．507倍（OR=1．507，95％CI：1．106～2．054）；携带T等位基因的慢性乙型肝炎患者血清TGF-β1水平显著高于不携带者（P〈0．05）。联合基因型分析发现，TGF-β1基因-509C／T、869T／C单核苷酸多态性存在着强烈的连锁不平衡（ID’I=0．891），与-509C／869T单倍型携带者比较，-509T／869C单倍型携带者显著增加了慢性乙型肝炎的发病风险（OR=1．663，95％CI：1．193-2．320）。结论TGF-β1基因-509C／T多态性和-509T／869C单倍型与慢性乙型肝炎的发病具有相关性，其中T等位基因可能是慢性乙型肝炎的遗传易感基因，携带T等位基因的个体可能通过促进TGF-β1的高度表达进而增加了慢性乙型肝炎的发病风险。

Objective To investigate the association of single nucleotide polymorphisms（SNP） and its haplotypes of transforming growth faetor-β1 （TGF-β1） gene with the susceptibility to chronic hepatitis B（CHB） in a Chinese population. Methods We analyzed two single nueleotide polymorphisms of TGF-β1 gene promoter -509C/ T and 869T/C（Leu10Pro） at exon one in 155 patients with CHB and 170 age and sex matched controls in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） strategy and DNA sequencing, and the serum level of TGF-β1 was determined by enzyme-linked immunoserbent assay （ELISA）. Frequency of haplotypes and linkage disequilibrium of TGF-β1 gene in different groups were analyzed by SHEsis programs. Results The distributions of TGF-β1 gene 869T/C polymorphism was not different between CHB and control group, but the TGF-β1 gene-509C/T polymorphism was significantly different（ P〈0.05）. The relative risk suffered from CHB of C allele was 1. 507 times of the T allele carriers （OR=1.507, 95% CI ：1.106-2.054）;the serum level of TGF-β1 T allele carriers was significantly higher than no carders（P〈0.05）. Consistent with the results of the genotyping analysis, TGF-β1-509C/T and 869T/C polymorphisms showed strong linkage disequilibrium（ID＇I =0.891）, the -509T/869C haplotype was associated with a significantly increased risk of NPC as compared with the -509C/869T haplotype （OR= 1. 663, 95% CI： 1. 193-2. 320）. Conclusion TGF-β1 gene -509C/T polymorphism and its haplotype are associated with HBV, and T allele is an important genetic sus- ceptibility gene for HBV. The risk of TGF-β1 T allele carriers maybe increase by enhancing the TGF-β1 expression in the pathogenesis of HBV.