维吾尔族和哈萨克族毒性弥漫性甲状腺肿患者子宫球蛋白相关蛋白1基因多态性研究

Single nucleotide polymorphisms of uteroglobin-related protein gene in Uygur and Kazak patients with Graves disease

目的 探讨新疆维吾尔族和哈萨克族毒性弥漫性甲状腺肿（Graves病）患者子宫球蛋白相关蛋白1（UGRP1）基因单核苷酸多态性（SNP）.方法 收集2010年1-7月新疆地区374例散发维吾尔族和哈萨克族Graves病患者（Graves病组）以及年龄相匹配的378名维吾尔族和哈萨克族健康对照者（对照组）,采集外周血白细胞抽提DNA,分析UGRP1 SNP位点,采用TaqMan探针技术,在Fluidigm EP1平台上进行等位基因和基因型分析,比较Graves病组和对照组基因型差异,并比较不同性别、是否有高血压、是否为复发、是否有胫前黏液性水肿、不同甲状腺肿大程度和突眼程度Graves病患者间基因型差异.结果 共分析UGRP1基因上33个SNP位点,其中rs 6859391位点GG、CC和CG型对照组分别为88.6％（335/378）、0.5％ （2/378）、10.9％（41/378）,Graves病组分别为94.4％（353/374）,0.3％ （1/374）和5.3％（20/374）,2组间差异有统计学意义（P＜0.05）;对照组和Graves病组G等位基因频率分别为94.0％（711/756）和97.1％（726/748）,C等位基因频率分别为6.0％（45/756）和2.9％（22/748）,C等位基因为维吾尔族和哈萨克族Graves病发生的保护性碱基（比值比=0.48,95％置信区间：0.28～0.82,P＜0.01）.不同临床特征Graves病患者rs 6859391位点基因类型差异均无统计学意义（均P＞0.05）.结论 UGRP1基因位点rs 6859391SNP可能参与新疆维吾尔族和哈萨克族人群Graves病的发生、发展。

Objective To explore the single nucleotide polymorphisms （SNPs） of uteroglobin-related protein （UGRP1） gene in Uygur and Kazak patients with Graves disease.Methods Totally 426 sporadic Uygur and Kazak patients of Graves disease （Graves disease group） and 387 age-matched healthy volunteers （control group） from January to July 2010 were enrolled.The DNA was extracted from peripheral white blood cells to analyze the UGRP1 SNP loci.The genotype was analyzed using TaqMan probe technique and Fluidigm EP1 platforms.In addition, the difference of genetype in Graves disease patients with different clinical indicators, including sex, blood pressure, recurrence, myxedema, degree of goiter and exophthalmos, were compared.Results A total of 33 SNPS loci of UGRP1 gene were analyzed;the allele and genotype allele frequencies of SNP loci rs6859391 showed differences between control group [GG genetype ： 88.6% （335/378）, CC genetype ： 0.5 % （2/378）, CG genetype： 10.9% （41/378）] and Graves group [GG genetype： 94.4% （353/374）, CC genetype： 0.3% （1/374）, CG genetype： 5.3% （20/374）] （P 〈 0.05）.In control group and Graves disease group, the ratio of G allele was 94.0% （711/756） and 97.1% （726/748） respectively;the ratio of C allele was 6.0% （45/756） and 2.9% （22/748） respectively.The C allele was a protective factor for Graves disease （odds ratio： 0.48, 95% confidence interval： 0.28-0.82, P 〈 0.01）.The genotype allele of rs 6859391 loci showed no statistical differences among Graves disease patients with different symptoms （all P 〉 0.05）.Conclusion SNP of UGRP1 gene locus and rs 6859391 may be involved in the occurrence and development of Graves disease in Uygur and Kazak people.