Tron François, Gilbert Danièle, Mouquet Hugo, Joly Pascal, Drouot Laurent, Makni Sondès, Masmoudi Hatem, Charron Dominique, Zitouni Mondher, Loiseau Pascale, Ben Ayed Mourad
Unité INSERM 519 - IFRMP 23, Hôpital Charles Nicolle, Faculté Mixte de Médecine et de Pharmacie, 22, Boulevard Gambetta, 76183 Rouen Cedex, France.
J Autoimmun. 2005 Jun;24(4):319-28. doi: 10.1016/j.jaut.2005.03.006.
Epidemiological studies performed in different ethnic populations and family studies, notably based on a partial phenotype of the autoimmune process, indicate that genetic factors are involved in the occurrence of pemphigus. However, the precise heritability remains uncertain in the absence of twin concordance rate studies. Among the different strategies available to identify genetic factors participating in autoimmune disease susceptibility, only population studies based on case-control design have been performed in pemphigus. These studies consistently showed that MHC locus, in particular HLA class II alleles, are associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the MHC locus may also participate in disease susceptibility as shown by studies using microsatellite markers across different regions of the MHC. It is likely that other non-MHC genes are involved in the pathogenesis of pemphigus. In particular, involvement of a polymorphic variant of desmoglein 1 gene was shown to be associated with pemphigus foliaceus and to interact in an epistatic manner with MHC class II genes to contribute to the autoimmune process. Other candidate genes to which a role can be assigned in the disease pathogenesis should be considered to design case-control or family-based association studies. Genome scan studies which require a large number of multiplex families to reach statistical power, should also be considered in the endemic form of pemphigus foliaceus because of the high number of familial cases.
在不同种族人群中开展的流行病学研究以及家族研究（尤其是基于自身免疫过程的部分表型）表明，遗传因素与天疱疮的发病有关。然而，由于缺乏双胞胎一致性率研究，确切的遗传度仍不确定。在可用于识别参与自身免疫性疾病易感性的遗传因素的不同策略中，天疱疮仅开展了基于病例对照设计的人群研究。这些研究一致表明，主要组织相容性复合体（MHC）位点，特别是人类白细胞抗原（HLA）Ⅱ类等位基因，与寻常型天疱疮和落叶型天疱疮相关。MHC位点的其他基因也可能参与疾病易感性，这在使用MHC不同区域微卫星标记的研究中得到了证实。很可能其他非MHC基因也参与了天疱疮的发病机制。特别是，桥粒芯糖蛋白1基因的一个多态性变体的参与被证明与落叶型天疱疮相关，并以上位性方式与MHCⅡ类基因相互作用，从而促进自身免疫过程。在设计病例对照或基于家族的关联研究时，应考虑其他在疾病发病机制中可能起作用的候选基因。由于落叶型天疱疮家族性病例数量较多，对于其地方性形式，也应考虑进行全基因组扫描研究，这类研究需要大量的多个成员的家庭才能达到统计学效力。
