中国汉族Graves病的一个主要易感位点定位于染色体5q31  

A major susceptibility locus locating in chromosome 5q31 for Graves′ disease in Chinese Han pedigrees

作　　者：金迎[1] 滕卫平[1] 贲松涛[2] 熊晓艳 张静 徐世杰 姚茵[4] 金力 陈家伦[5] 黄薇 

机构地区：[1]中国医科大学附属第一医院内分泌代谢科,沈阳110001 [2]中国医科大学公共卫生学院 [3]国家人类基因组南方研究中心 [4]美国巴尔的摩约翰霍普金斯大学布鲁穆博格公共卫生学院流行病学系 [5]上海第二医科大学附属瑞金医院

出　　处：《中华内分泌代谢杂志》2004年第2期100-103,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目(39970350);美国中华医学基金会资助项目(98688IITD);国家自然科学基金重大项目资助(39896200);国家基础研究重大项目资助(G1998051002)

摘　　要：目的　确定中国人Graves病 (GD)的染色体易感区。方法　采用 2 77个高度多态 (平均间距约为 13cM )的微卫星标记对 5 4个中国汉族GD多发家系的 3 2 2名个体做全基因组扫描研究。分别计算疾病在呈显性及隐性遗传的各外显率下 ,各微卫星的两点LOD值及多点LOD值 ,并计算多点非参数连锁(NPL)值。结果　参数法连锁分析显示染色体 5q3 1区的D5S43 6的两点LOD值与多点LOD值均最高 ,分别为 2 .8和 2 .3。为了进一步确定该区域在GD发生中的作用 ,在D5S43 6两侧又增加了 4个微卫星做基因分型和连锁分析 ,在D5S2 0 90处得到了最大两点LOD值 4.3 1和最大多点LOD值 4.12 (具有遗传异质性 ,α^ =0 .3 8)。多点非参数法连锁分析也显示D5S2 0 90的NPL值最高 ,为 2 .66(P =0 .0 0 1) ,同样支持该位点与GD相连锁。结论　GD的一个主要易感位点位于染色体 5 q3 1区 ;在GD中存在遗传异质性。Objective To identify chromosomal regions contributing to Graves′ disease (GD) in Chinese. Methods Using 277 highly polymorphic microsatellite markers with an average inter-marker spacing of 13 centimorgans, a genome-wide scan was conducted on 322 individuals from 54 Chiense Han multiplex GD pedigrees. Assuming both dominant and recessive models, two-point and multi-point LOD scores of various microsatellite markers were calculated under different levels of penetrance. Multipoint nonparametric linkage (NPL) score was also calculated. Results Parametric linkage analysis showed a strong evidence for linkage at D5S436 on chromosome 5q31 with a maximum two-point LOD score of 2.8 and a maximum multipoint LOD score of 2.3. To further assess the significance of this suggestive finding, four additional markers around D5S436 in this chromosome region were typed, and a maximum two-point LOD score of 4.31 and a maximum multipoint LOD score of 4.12 were obtained for marker D5S2090 (with heterogeneity, α^=0.38). Nonparametric multipoint analysis also showed the peak NPL score 2.66 at D5S2090 (P=0.001) , which also supports the evidence for linkage at this locus. Conclusion A susceptibility locus for GD locates in chromosome 5q31, which supports the existence of genetic heterogeneity in GD.

关 键 词：中国 汉族 GRAVES病 易感位点 染色体 5q31 

分 类 号：R581.1[医药卫生—内分泌]