弥漫性甲状腺肿伴甲状腺功能亢进症致病易感基因识别鉴定研究的现状  

Recent progress in identification of candidate genes of Graves＇ disease

作　　者：宋怀东[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院分子医学中心,上海市内分泌代谢病研究所,200025

出　　处：《中华内分泌代谢杂志》2011年第12期961-966,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金（30971595,30971383,81100553）

摘　　要：经过半个世纪对弥漫性甲状腺肿伴甲状腺功能亢进症（Graves’disease,GD,甲亢）候选基因在小样本人群中的研究,提供了不少相互矛盾的结果.在这些研究中,仅仅证实主要组织相容性复合物（MHC）是甲亢的一个致病易感位点,因为这个位点对甲亢发生影响较大.应用以低密度的微卫星标志进行全基因组连锁分析,虽然发现了一些甲亢的致病易感区段,但并未能识别真正的甲亢致病易感基因.随后由于大量单核苷酸多态性（SNP）的发现及其标签SNP（Tag SNP）技术的出现,人们对候选基因上的Tag SNP在大样本人群中的分析,发现了一些真正的甲亢致病易感基因,包括免疫相关的基因如MHC、CTLA4、SCGB3A2/UGRP1和FCRL3以及一个甲状腺特异的基因TSHR（促甲状腺素受体基因）.同时,也发现了一些还有争议但需要进一步证实的甲亢易感基因如PTPN22和甲状腺球蛋白基因等.在不久的将来,全基因组关联分析和全基因组再测序技术,在甲亢易感基因识别鉴定中的应用,无疑将会促进大量甲亢易感基因的发现,加深人们对甲亢发病机制的理解.Intensive but quite chaotic and decentralized candidate gene studies on susceptibility to Graves＇ disease （ GD ） carried out in small size population in the past half century have provided a quantity of inconsistent data,which,however,resulted in finding of a proven association of GD with the MHC class Ⅱ region that exerts a major effect on the genetics of GD.Using low-resolution microsatellite-based human genome-wide linkage analysis,several regions of linkage harboring putative susceptibility variants but no gene susceptibility to GD were identified.Further,high throughput genotyping of large population cohorts with help of high dense panels of single nucleotide polymorphisms （SNPs） and application of advanced tools for analysis of extended blocks of linkage disequilibrium within a candidate gene （ tagging SNP,etc.） have found several genes susceptible to GD,including immune-related genes such as MHC,CTLA4,SCGB3A2/UGRP1,FCRL3,and thyroid specific genes （ such as TSHR,etc.）.Less consistent results have been obtained in cases of PTPN22 and thyroglobulin.In the nearest future,implementation of even more robust technology such as genome-whole associated analysis （GWAS） and whole-genome re-sequencing are expected to catch more genes susceptibilities to GD.

关 键 词：格雷夫斯病 多态现象 遗传 基因组学 

分 类 号：R581[医药卫生—内分泌]