上海地区I型自身免疫性肝炎与HLA-DRB1等位基因的相关性研究

Relationship between type I autoimmune hepatitis and alleles of HLA-DRBl in Chinese patients of Shanghai area

目的 分析 HLA—DRB1等位基因与上海地区I型自身免疫性肝炎（AIH）的相关性,探讨 AIH的遗传易感背景。方法 采用序列特异性多聚酶链反应（PCR—SSP）,对32例I型AIH患者和48例健康对照者进行HLA—DRB1等位基因及有关基因亚型的分析。结果HLA—DR4基因频率在I型AIH患者中较健康对照组显著增高[46.9％与20.8％;相对危险度（RR）=3.35,x2=5.99,P=0.014]。其他等位基因在两组间差异无显著性。进一步对HLA-DR4等位基因亚型的分析表明,I型AIH患者组DRB1＊0405的基因频率较健康对照组有增加趋势（21.9％与6.3％,x2=4.23,P=0.04,但 Pc=0.08）。HLA—DRβ分子的第3等位基因高变区第71位精氨酸残基的频率在I型AIH患者中显著增高（46.9％与 18.8％,x2=7.14,P=0.008）。结论 上海地区I型 AIH的发病与HLA—DR4以及HLA—DRB1第3高变区DR71位精氨酸残基相关。

Objective To analyze the association between alleles of HLA-DRB1 and type I autoimmune hepatitis (AIH) in patients from Shanghai, China. Methods In 32 Chinese patients with type I AIH and 48 healthy controls in Shanghai area, polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) was performed to examine the association of the alleles of HLA-DRB 1 and its subtypes with type I AIH. Results HLA-DRB 1 typing by PCR-SSP showed that DR4 had a significantly increased frequency among patients with AIH versus healthy control (46.9% versus 20.8%; relative risk=3.35, x2=5.99, P=0.014). No other alleles differed significantly between the two groups. In subtypes of DRB1 *04, there was a trend for an increase in gene frequency of DRB1 *0405 increased in patients with type I AIH versus healthy controls (21.9% vs 6.3%, x2=4.23, P=0.04, but Pc=0.08). The frequency of arginine at position HLA-DRβ 71 of third hypervariable region significantly increased among patients with AIH versus healthy control (46.9% versus 18.8%, x2=7.14, P=0.008). Conclusions Type I AIH in Chinese patients of Shanghai area is associated with HLA-DR4 and arginine at position DR β71 of third hypervariable region.