人类白细胞抗原-DRB1基因多态性与妊娠期肝内胆汁淤积症的相关性研究

Relationship between human leukocyte antigen-DRB1 allele gene polymorphism and intrahepatic cholestasis of pregnancy

目的 探讨人类白细胞抗原 (HLA) DRB1基因多态性与妊娠期肝内胆汁淤积症 (ICP)的关系。方法 采用聚合酶链反应序列寡核苷酸 (PCR SSO)探针杂交法对 42例ICP患者 (ICP组 )和 5 6例正常孕妇 (对照组 )进行HLA DRB1等位基因分型 ,比较其基因频率及其与临床表型之间的关系。同时对ICP组孕妇的肝功能及甘胆酸盐水平进行检测。结果 两组孕妇中 ,HLA DR9、DR12、DR4基因频率均较高。ICP组孕妇中共检出 14例HLA DR6等位基因 ,对照组仅检出 4例HLA DR6等位基因。ICP组中HLA DR6等位基因频率为 16 7% ,对照组为 3 6% ,两组比较 ,差异有极显著性 (P<0 0 1)。其余各等位基因频率两组比较 ,差异均无显著性 (P >0 0 5 )。未发现ICP组孕妇HLA DR6基因与肝功能及甘胆酸盐水平有相关关系。结论 ICP患者HLA DR6基因可能是ICP发病的易感基因之一。

Objective To study the relationship between human leukocyte antigen-DRB1 (HLA-DRB1) allele genes polymorphism and intrahepatic cholestasis of pregnancy (ICP). Methods Forty-two patients with ICP were tested for HLA-DRB1 allele genes polymorphism with the polymerase chain reaction technique and sequence specific oligonucleotide (PCR-SSO) probes hybridization, 56 normal pregnant women as control group were also tested. In addition, the phenotype frequencies of HLA-DRB1 alleles were compared with it′s clinical character in patients with ICP. Results The higher frequencies were observed for alleles DR9, DR12 and DR4 in both groups. DR6 alleles were detected in 14 cases out of 42 patients. Patients with ICP had a significantly higher frequency of the allele DR6 when compared to control group (16.7% vs 3.6%), with a relative risk (RR) as 6.5 (P <0.01). No significant differences were observed between the frequencies of other detected HLA-DRB1 alleles in both groups. There was no association between HLA-DR6 allele and the level of liver function and cholylglycine in ICP. Conclusion The study showed that HLA-DR6 gene might be one of the susceptibility genes to ICP.