人类白细胞抗原
单核苷酸多态性
主要组织相容性复合体
插补(统计学)
大疱性类天疱疮
SNP公司
优势比
等位基因
皮肌炎
免疫学
单倍型
医学
遗传学
生物
抗原
基因
内科学
基因型
抗体
缺少数据
机器学习
计算机科学
作者
Wencheng Fan,Zhuo Li,Yirui Wang,Chang Zhang,Hao Líu,Daiyue Wang,Yuanming Bai,Sihan Luo,Yuanyuan Li,Qin Qin,Weiwei Chen,Yong Liang,Qi Zhen,Yafen Yu,Huiyao Ge,Yan Mao,Lu Cao,Ruixue Zhang,Xia Hu,Yanxia Yu,Bao Li,Liangdan Sun
标识
DOI:10.1111/1346-8138.16499
摘要
As autoimmune skin diseases, both bullous pemphigoid (BP) and dermatomyositis (DM) show significant associations with the major histocompatibility complex (MHC) region. In fact, the coexistence of BP and DM has been previously reported. Therefore, we hypothesized that there may be a potential genetic correlation between BP and DM. Based on data for 312 BP patients, 128 DM patients, and 6793 healthy control subjects, in the MHC region, we imputed single-nucleotide polymorphisms (SNP), insertions and deletions (INDEL), and copy number variations (CNV) using the 1KGP phase 3 dataset and amino acids (AA) and SNP using a Han-MHC reference database. An association study revealed the most significant SNP associated with BP, namely, rs580921 (p = 1.06E-08, odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.37-1.90), which is located in the C6orf10 gene, and the most significant classic human leukocyte antigen (HLA) allele associated with DM, namely, HLA-DPB1*1701 (p = 6.56E-10, OR = 3.61, 95% CI = 2.40-5.42). Further stepwise regression analyses with rs580921 identified a threonine at position 163 of the HLA-B gene as a new independent disease-associated AA, and HLA-DPB1*1701 indicated that no loci were significant. Three-dimensional ribbon models revealed that the HLA-B AA position 163 (p = 3.93E-07, OR = 1.64, 95% CI = 1.35-1.98) located in the α2 domain of the HLA-B molecule was involved in the process of specific antigen presentation. The calculations showed that there was no significant genetic correlation between BP and DM. Our study identified three significant loci in the MHC region, proving that the HLA region was significantly correlated with BP and DM separately. Our research highlights the key role of the MHC region in disease susceptibility.