Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
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DOI：
10.1056/nejmoa0908547
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发表时间：
2010-05-06
期刊：
影响因子：
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通讯作者：
Spritz RA
中科院分区：
文献类型：
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作者：
Jin Y;Birlea SA;Fain PR;Gowan K;Riccardi SL;Holland PJ;Mailloux CM;Sufit AJ;Hutton SM;Amadi-Myers A;Bennett DC;Wallace MR;McCormack WT;Kemp EH;Gawkrodger DJ;Weetman AP;Picardo M;Leone G;Taïeb A;Jouary T;Ezzedine K;van Geel N;Lambert J;Overbeck A;Spritz RA
泛发性白癜风是一种自身免疫性疾病，其特征是黑素细胞丢失，导致皮肤和毛发斑片状脱色，并与其他自身免疫性疾病的风险升高相关。为了确定泛发性白癜风易感基因，我们进行了全基因组关联研究。我们对1514名欧洲白色（CEU）血统的泛发性白癜风患者进行了579,146个单核苷酸多态性（SNP）基因分型，并将这些基因型与2813名CEU患者的公开对照基因型进行了比较。然后，我们在两个重复组中测试了50个SNP，一个重复组包括677名独立的CEU患者和1106名CEU对照，另一个重复组包括183名CEU单纯性三重奏和332个CEU多发性家族。我们检测到泛发性白癜风与先前与其他自身免疫性疾病相关的几个位点的SNP之间存在显著关联。其中包括编码主要组织相容性复合物I类分子的基因（P = 9.05×10−23）和II类分子（P = 4.50×10−34）、PTPN 22（P = 1.31×10−7）、LPP（P = 1.01×10−11）、IL2RA（P = 2.78×10−9）、UBASH3A（P = 1.26×10−9）和C1QTNF 6（P = 2.21×10−16）。我们还检测到泛发性白癜风与另外两个免疫相关基因座（RERE（P = 7.07×10−15）和GZMB（P = 3.44×10−8））以及编码酪氨酸酶的TYR（P = 1.60×10−18）基因座的SNP之间的关联。我们观察到泛发性白癜风和涉及多个基因的标记物之间的关联，其中一些与其他自身免疫性疾病相关，一个（TYR）可能介导靶细胞特异性，并表明白癜风易感性和黑色素瘤易感性之间的相互排斥关系。
Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P = 9.05×10−23) and class II molecules (P = 4.50×10−34), PTPN22 (P = 1.31×10−7), LPP (P = 1.01×10−11), IL2RA (P = 2.78×10−9), UBASH3A (P = 1.26×10−9), and C1QTNF6 (P = 2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P = 7.07×10−15) and GZMB (P = 3.44×10−8), and in a locus containing TYR (P = 1.60×10−18), encoding tyrosinase. We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma.