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首页> 外文期刊>Pigment cell research >HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset
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HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset

机译：HLA II类单倍型DRB1 * 04-DQB1 * 0301导致家族性白癜风和早期疾病发作的风险

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摘要

Generalized vitiligo is a common autoimmune disorder characterized by white patches of skin and overlying hair caused by loss of pigment-forming melanocytes from involved areas. Familial clustering of vitiligo is not uncommon, and patients and their relatives are at increased risk for a specific complex of other autoimmune diseases. Compared with sporadic vitiligo, familial vitiligo is characterized by earlier disease onset and greater risk and broader repertoire of autoimmunity, suggesting a stronger genetic component, and perhaps stronger associations with specific alleles. To determine whether the major histocompatibility complex (MHC) contributes to the familial clustering of vitiligo and vitiligo-associated autoimmune/autoinflammatory diseases, we performed case-control and family-based association analyses of HLA class II-DRB1 and -DQB1 alleles and haplotypes in affected probands and their parents from 76 European-American Caucasian families with familial vitiligo. Affected probands showed a significantly increased frequency of DRB1*04-DQB1*0301 and a significantly decreased frequency of DRB1*15-DQB1*0602 compared with a large sample of reference chromosomes. Family-based association analyses confirmed these results. Probands with DRB1*04-DQB1*0301 developed vitiligo an average of 13.32 yr earlier than probands with DRB1*15-DQB1*0602. Overall, our results indicate that specific MHC-linked genetic variation contributes to risk of familial vitiligo, although HLA does not completely explain familial clustering of vitiligo-associated autoimmune/autoinflammatory diseases.
机译：广泛性白癜风是一种常见的自身免疫性疾病，其特征是皮肤和上层毛发呈白色斑块，是由相关区域的色素形成性黑素细胞损失引起的。白癜风家族聚集并不少见，患者及其亲属患其他自身免疫性疾病的特定复合体的风险也增加。与散发性白癜风相比，家族性白癜风的特征是疾病发作较早，自体免疫的风险更高和范围更广，这表明其遗传成分更强，也许与特定等位基因的关联更强。为了确定主要的组织相容性复合物（MHC）是否有助于白癜风和白癜风相关的自身免疫性/自身炎症性疾病的家族性聚集，我们进行了病例对照和基于家庭的HLA II-DRB1和-DQB1等位基因及单倍型关联分析受影响的先证者及其父母来自76个患有白种人白癜风的欧美白种人家庭。与大量参考染色体样本相比，受影响的先证者显示DRB1 * 04-DQB1 * 0301的频率显着增加，而DRB1 * 15-DQB1 * 0602的频率显着降低。基于家庭的关联分析证实了这些结果。具有DRB1 * 04-DQB1 * 0301的先证者比患有DRB1 * 15-DQB1 * 0602的先证者平均早发白癜风13.32年。总的来说，我们的结果表明，尽管HLA不能完全解释白癜风相关的自身免疫性/自身炎症性疾病的家族性聚集，但特定的MHC相关遗传变异有助于家族性白癜风的发生。

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