A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families

被引:58
作者
Chen, JJ
Huang, W
Gui, JP
Yang, S
Zhou, FS
Xiong, QG
Wu, HB
Cui, Y
Gao, M
Li, W
Li, JX
Yan, KL
Yuan, WT
Xu, SJ
Liu, JJ
Zhang, XJ
机构
[1] Anhui Med Univ, Inst Dermatol, Affiliated Hosp 1, Hefei, Anhui, Peoples R China
[2] Anhui Med Univ, Dept Dermatol, Affiliated Hosp 1, Hefei, Anhui, Peoples R China
[3] Key Lab Genome Res, Hefei, Anhui, Peoples R China
[4] Chinese Natl Human Genome Ctr, Shanghai, Peoples R China
[5] Railway Hosp, Vitiligo Clin, Xiangfan, Hubei, Peoples R China
[6] Genome Inst Singapore, Singapore, Singapore
关键词
D O I
10.1086/430279
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far-on chromosomes 1p31, 6p21, 7q, 8p, and 17p13-in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at least two affected siblings, and we identified interesting linkage evidence on 1p36, 4q13-q21, 6p21-p22, 6q24-q25, 14q12-q13, and 22q12. Subsequently, to extract more linkage information, we investigated our initial genomewide linkage findings in a follow-up analysis of 49 new families and additional markers. Our initial genomewide linkage analysis and our subsequent follow-up analysis have identified a novel linkage to vitiligo on 4q13-q21, with highly significant linkage evidence (a nonparametic LOD score of 4.62 [P = .000003] and a heterogeneity LOD score of 4.01, under a recessive inheritance model), suggesting that 4q13-q21 likely harbors a major susceptibility locus for vitiligo in the Chinese population. We observed a minimal overlap between the linkage results of our current genomewide analysis in the Chinese population and the results of previous analyses in white populations, and we thus hypothesize that, as a polygenic disorder, vitiligo may be associated with great genetic heterogeneity and a substantial difference in its genetic basis between ethnic populations.
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页码:1057 / 1065
页数:9
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