中国北方汉族格雷夫斯病主要易感位点的检测及意义

目的　探讨和确定位于染色体 6p2 1区的人类主要组织相容性复合体 (MHC)区是否为中国北方汉族Graves病 (GD)的主要易感位点。方法　采用 4个高度多态且覆盖整个染色体 6p2 1区的微卫星标记筛查 5 4个 (32 2人 )中国北方汉族GD多发家系。分别计算疾病在呈显性及隐性遗传的外显率下 ,各微卫星的两点及多点Lod值 ,并计算多点非参数连锁值。结果　在每种遗传模式下 ,各微卫星的两点 (θ =0 )及多点Lod值均小于 - 2。无任何家系在所设定的遗传模式下两点或多点Lod值达到或超过 1.0。在设定存在遗传异质性的情况下 ,最大多点Lod值为 0 .5 5 ,阳性连锁家系占 2 9%。多点非参数连锁值差异均无显著意义 (P >0 .0 5 )。结论　染色体 6p2 1区不存在与中国北方汉族GD相连锁的基因位点。MHC区不是中国北方汉族GD的主要易感位点。

The human major histocompatibility complex region is not a major susceptibility locus for Graves disease among the Hans in north of China

OBJECTIVE: To determine if the human major histocompatibility complex (MHC) region located on chromosome 6 p21 is a major susceptibility locus for Graves' disease (GD) among the Hans in North of China. METHODS: Four highly polymorphic microsatellite markers spanning the entire region of chromosome 6 p21 were employed to screen the DNA from blood samples of 54 Han multiplex families with GD (322 individuals) in Liaoning Province, northeast China. Tow-point and multi-point Lod scores were calculated under different levels of penetrance, assuming both dominant and recessive models. Multipoint nonparametric linkage (NPL) scores were also calculated. RESULTS: The two-point Lod scores (theta = 0) and multipoint Lod scores for the 4 microsatellites were all less than -2 for all the markers tested, at all levels of penetrance, and in both the dominant and recessive modes of inheritance. No family showed a two-point Lod score or a multipoint Lod score of 1.0 or even larger under the assumed inheritance models. The maximum multipoint Lod score was 0.55 under the assumption of genetic heterogeneity, with the proportion of linked families of 29%. P values of greater than 0.05 were observed for all the multipoint NPL scores obtained. CONCLUSION: No locus linked with GD among the Hans in North of China exists on chromosome 6 p21. Human MHC region is not a major susceptibility locus for northern Chinese Han Graves' disease.