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

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，χ^2=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％，χ^2=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AHI患者中显著增高（46.9%与18.8%,χ^2=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DR7位精氨酸残基相关。

Relationship between type I autoimmune hepatitis and alleles of HLA-DRB1 in Chinese patients of Shanghai area

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-DRB1 and its subtypes with type I AIH. RESULTS: HLA-DRB1 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, chi(2)=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%, chi(2)=4.23, P=0.04, but Pc=0.08). The frequency of arginine at position HLA-DR beta 71 of third hypervariable region significantly increased among patients with AIH versus healthy control (46.9% versus 18.8%, chi(2)=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 beta 71 of third hypervariable region