Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 22, Issue 2, Pages 230-234Publisher
WILEY
DOI: 10.1111/j.1755-148X.2009.00543.x
Keywords
CTLA4; Vitiligo; genetic association; SNP; meta-analysis
Categories
Funding
- National Institutes of Health [AR45584, AI46374, DK57538]
- American Skin Association
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Several lines of evidence have implicated the gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) in susceptibility to various autoimmune diseases. However, published studies of genetic association between CTLA4 polymorphisms and vitiligo have yielded conflicting results. Here, we describe two new genetic association studies of CTLA4 single-nucleotide polymorphisms (SNPs) and generalized vitiligo in two independent Romanian Caucasian (CEU) case-control cohorts. The first study, of SNPs rs1863800, rs231806, rs231775, rs3087243, rs11571302, rs11571297, and rs10932037, showed no allelic, genotypic, or haplotypic association with generalized vitiligo. The second study, of SNP rs231775, likewise showed no significant association. To enhance statistical power over that of any individual study, we carried out a meta-analysis that incorporated these two new studies and all other published genetic association studies of CTLA4 SNPs and vitiligo in CEU populations. While there was no association with vitiligo overall, the meta-analysis showed significant association of SNP rs231775 in that subgroup of vitiligo patients who also had other concomitant autoimmune diseases. Similarly, there was near-significant association in this same patient subgroup with several other CTLA4 SNPs that are in linkage disequilibrium with rs231775. Our results indicate that the association of CTLA4 with vitiligo is weak, and indeed may be secondary, driven by primary genetic association of CTLA4 with other autoimmune diseases that are epidemiologically associated with vitiligo.
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