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A Novel Linkage to Generalized Vitiligo on 4q13-q21 Identified in a Genomewide Linkage Analysis of Chinese Families

2005; Elsevier BV; Volume: 76; Issue: 6 Linguagem: Inglês

10.1086/430279

1537-6605

Jianjun Chen, Wei Huang, Jin-Ping Gui, Sen Yang, Fusheng Zhou, Quan-Geng Xiong, Hongbo Wu, Yong Cui, Min Gao, Wěi Li, Jinxian Li, Kai‐Lin Yan, Wentao Yuan, Shi-Jie Xu, Jianjun Liu, Xuejun Zhang,

Herpesvirus Infections and Treatments

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.