口腔扁平苔藓患者的CIITA基因单倍型分析

Haplotype Analysis of CIITA Gene in Oral Lichen Planus

目的:分析CIITA基因中单核苷酸多态性(Single Nucleotide Polymorphism,SNP)的单倍型与口腔扁平苔藓(Oral Lichen Planus,OLP)之间的关系,并探讨计算单倍型的新方法。方法:在得到42名患者与86名对照的CIITA基因中15个SNP位点的信息后,通过Haploview和SHEsis软件以及本研究组设计的频数计数法进行单倍型分析。组间比较使用χ2检验,并以P=0.05作为统计检验标准。结果:在本研究群体中,CIITA基因上的15个SNP位点能够形成两个单体域(haploblock),其中由位点rs6498124,rs11647384和rs4774所组成的单倍型GAC在三种单倍型分析方法中均显示出显著的统计学差异(Haploview:Chi2=6.127,P=0.013;SHEsis:Chi2=6.469 P=0.011;频数计数法:Chi2=5.460,P=0.019)。结论:在由CIITA基因的SNP位点rs6498124,rs11647384,rs4774组成的单体域中,单倍型GAC对OLP的患病具有潜在的保护性。频数计数法显示,rs4774位点本身的保护性及其与同一单体域内另外两个位点之间的完全连锁不平衡关系是单体型GAC显示出保护性的主要依据。提示单倍型对疾病易感性的解释在于其中的特定SNP位点等位基因型,及其该位点与其它相关位点间的连锁不平衡关系。

Objective： This study analyses the relationship between OLP and haplotype composed of SNPs in CIITA, and develops a new method of haplotype analysis. Methods： With the SNPs information of a case group of 42 and a control group of 86, we use haploview and SHEsis to analyze haplotype. When compare group data. Chi-square test is used which takes p=0.05 as the statistical significance threshold. Results： In the cohort, 15 SNPs of the CIITA gene formed 2 haploblocks, in which rs6498124, rs11647384, rs4774 compose a haplotype GAC. This haplotype showed statistical significance in each analyzing method（Haploview： Chi2=6.127, P=0.013SHEsis： Chi2= 6.469, P=0.011 frequency-counting： Chi2=5.460, P=0.019）. Conclusions： In a haploblock composed of rs6498124,rs11647384 and rs4774 in CIITA, the haplotype GAC showed potential protection for OLP. The analysis from frequency-counting showed that the protection of rs4774 itself and its linkage disequilibrium relationship with other sites in the same haploblock contribute to the protection of haplotype GAC. And indicate that haplotype explanation for disease susceptivity may rely on the allelotype of certain significant SNP site and its linkage disequilibrium relationship with other related sites.