CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data.
CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data.
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DOI：
10.1111/j.1755-148x.2009.00543.x
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发表时间：
2009-04
影响因子：
4.3
通讯作者：
Spritz RA
中科院分区：
文献类型：
--
作者：
Birlea SA;Laberge GS;Procopciuc LM;Fain PR;Spritz RA
一些证据表明，编码细胞毒性T淋巴细胞抗原4（CTLA 4）的基因与多种自身免疫性疾病的易感性有关。然而，已发表的CTLA4多态性与白癜风之间遗传关联的研究产生了相互矛盾的结果。在这里，我们描述了两个新的CTLA4单核苷酸多态性（SNPs）和泛发性白癜风在两个独立的罗马尼亚白人（CEU）病例对照队列的遗传关联研究。第一项研究，SNPs rs1863800，rs231806，rs231775，rs3087243，rs11571302，rs11571297，和rs10932037，显示没有等位基因，基因型，或单倍型与泛发性白癜风。第二项研究，SNP rs231775，同样没有显示出显着的关联。为了增强任何单项研究的统计能力，我们进行了一项荟萃分析，将这两项新研究和所有其他已发表的CEU人群中CTLA4 SNP与白癜风的遗传关联研究纳入其中。虽然总体上与白癜风没有关联，但荟萃分析显示SNP rs231775在白癜风患者亚组中具有显著关联，这些患者还患有其他伴随的自身免疫性疾病。类似地，在同一患者亚组中，与rs231775连锁不平衡的几个其他CTLA4 SNP存在接近显著的关联。我们的研究结果表明，CTLA 4与白癜风的关联很弱，实际上可能是继发性的，由CTLA 4与其他与白癜风流行病学相关的自身免疫性疾病的原发性遗传关联驱动。
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.