A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families.
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.
Chen
Jian-Jun
JJ
Institute of Dermatology and Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Huang
Wei
W
Gui
Jin-Ping
JP
Yang
Sen
S
Zhou
Fu-Sheng
FS
Xiong
Quan-Geng
QG
Wu
Hong-Bo
HB
Cui
Yong
Y
Gao
Min
M
Li
Wei
W
Li
Jin-Xian
JX
Yan
Kai-Lin
KL
Yuan
Wen-Tao
WT
Xu
Shi-Jie
SJ
Liu
Jian-Jun
JJ
Zhang
Xue-Jun
XJ
D002681:China / Q000453:epidemiology; D002894:Chromosomes, Human, Pair 4; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D009679:Nuclear Family; D010375:Pedigree; D018709:Statistics, Nonparametric; D014820:Vitiligo / Q000453:epidemiology* / Q000235:genetics*
D005819:Genetic Markers