中国汉族人群MHC区域与胃癌易感性的关联

  目的  探讨主要组织相容性复合体(major histocompatibility complex, MHC)区域遗传变异与胃癌易感性的关联。  方法  采用病例对照研究设计，以中国汉族人群MHC参考数据集为参照，利用SNP2HLA v1.0.3软件对MHC区域进行基因型填补；应用Logistic回归分析模型鉴定MHC区域中与胃癌易感性存在关联的遗传变异；基于公共数据库，通过系统功能注释探索MHC区域内的易感基因和功能性遗传变异。  结果  本研究发现，rs2517714为MHC区域与胃癌发生风险独立关联的遗传位点(OR=1.13, P=2.70×10-8)；功能注释显示位于HLA-A基因外显子区域的氨基酸多态性位点及单核苷酸多态性(single nucleotide polymorphism, SNP)可能会影响HLA-A蛋白稳定性；同时，非编码区的功能性遗传变异rs9295829可能通过影响所在区域增强子活性，从而远程调控HLA-A基因表达，共同影响易感基因HLA-A的功能。  结论  MHC区域致病性遗传变异通过影响易感基因HLA-A功能，从而影响胃癌易感性。

Association between MHC region and gastric cancer susceptibility in Han Chinese

  Objective  To investigate the association between genetic variants in the major histocompatibility complex (MHC) region and gastric cancer (GC) susceptibility.  Methods  Based on a case-control study, MHC region was imputed with SNP2HLA v1.0.3 software by using the Han-MHC database as a reference panel. Logistic regression analysis model was used to identify the independent genetic loci associated with GC susceptibility in the MHC region. Functional annotation of the MHC region was based on online public databases and performed to find the susceptibility gene and potential functional variants.  Results  We found that rs2517714 was the only independent association signal associated with GC risk in the MHC region (OR=1.13, P=2.70×10-8). The results of functional annotation showed that HLA amino acid polymorphisms and single nucleotide polymorphisms (SNPs) located in the exon region of HLA-A may affect the stability of HLA-A protein. The SNP rs9295829 located in a non-coding region could remotely regulate the expression of HLA-A by affecting enhancer activity.  Conclusion  Functional genetic variations in the MHC region may affect the function of the susceptibility gene HLA-A to modulate GC susceptibility.