Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus
Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus
复制标题
落叶型天疱疮 DSG1 与 HLA II 类基因的上位性
作者：
P. Martel;D. Gilbert;M. Busson;P. Loiseau;V. Lepage;L. Drouot;E. Delaporte;C. Prost;Pascal Joly;D. Charron;F. Tron
落叶型天疱疮（PF）是一种罕见的严重的皮肤自身免疫性疾病，由针对桥粒粘附糖蛋白1（DSG 1）的自身抗体引起。我们以前表明，DSG 1基因是多态性的，并在位置809编码同义T/C单核苷酸多态性与PF。为了确定是否发生疾病的复杂的遗传相互作用的结果，我们同时检查了主要组织相容性复合体（MHC）II类和DSG 1多态性PF易感性的贡献。我们对31例PF患者和84名健康对照进行的分析首次证实了先前报道的PF中常见的DRB 1 *04和DRB 1 *14遗传背景以及个体化DRB 1 *0102、DRB 1 *0402和DRB 1 *0406以及DRB 1 *1404作为法国白人PF患者的易感性MHC II类等位基因。C/C（809）基因型与PF的发生有关。DRB 1 *04等位基因和C/C（809）基因型相互作用，赋予更高的易感性PF。这些数据表明，在PF易感性的个体基因之间的上位性的作用，并说明遗传器官特异性自身免疫性疾病的复杂性。
Pemphigus foliaceus (PF) is a rare and severe cutaneous autoimmune disease caused by autoantibodies directed against desmoglein 1 (DSG1), a desmosomal adhesion glycoprotein. We previously showed that the DSG1 gene is polymorphic and that a coding synonymous T/C single nucleotide polymorphism at position 809 is associated with PF. To determine whether the disease occurred as a consequence of complex genetic interactions, we simultaneously examined the contribution of major histocompatibility complex (MHC) class II and DSG1 polymorphisms to PF susceptibility. Our analysis performed in 31 PF patients and 84 healthy controls first confirmed the previously reported common DRB1*04 and DRB1*14 genetic background in PF and individualized DRB1*0102, DRB1*0402 and DRB1*0406, and DRB1*1404 as susceptibility MHC class II alleles in French Caucasian PF patients. It also showed that the C/C(809) genotype was associated with PF. Combined analysis of HLA class II and DSG1 polymorphisms with several distinct statistical methods including logistic regression, showed that the DRB1*04 allele and the C/C(809) genotype interact to confer a higher susceptibility to PF. These data demonstrate the role of epistasis between individual genes in PF susceptibility and illustrate the genetic complexity of organ-specific autoimmune diseases.
登录
查看更多内容
DOI：
10.1073/pnas.92.25.11935
发表时间：
1995-12
影响因子：
11.1
作者：
Kai W. WUCHERPFENNIGt;Bei Yut;Kailash BHOLt;Dimitri S. Monos;Elias Argyris;W. Robert;Karr;A. R. AHMEDt;J. L. STROMINGERt
通讯作者：
Kai W. WUCHERPFENNIGt;Bei Yut;Kailash BHOLt;Dimitri S. Monos;Elias Argyris;W. Robert;Karr;A. R. AHMEDt;J. L. STROMINGERt
DOI：
10.1016/s0190-9622(97)80127-2
发表时间：
1997-08-01
影响因子：
13.8
作者：
Jiao, D;Bystryn, JC
通讯作者：
Bystryn, JC
DOI：
10.1073/pnas.95.25.14875
发表时间：
1998-12-08
影响因子：
11.1
作者：
Gaffney, PM;Kearns, GM;Behrens, TW
通讯作者：
Behrens, TW
部分寻常型天疱疮患者的 T 淋巴细胞对桥粒芯糖蛋白 3 和桥粒芯糖蛋白 1 均有反应。
DOI：
10.1111/1523-1747.ep12340738
发表时间：
1997
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Lin,MS;Swartz,SJ;Lopez,A;Ding,X;Fairley,JA;Diaz,LA
通讯作者：
Diaz,LA