HLA-DQB1 和 HLA-DRB1 变异与成人潜伏自身免疫性糖尿病易感性相关：等位基因组之间的相对易感性效应。
HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups.
机构信息
Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, Guangdong 523808, China.
The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong 523808, China.
出版信息
Genes (Basel). 2019 Sep 13;10(9):710. doi: 10.3390/genes10090710.
Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case-control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB102 (odds ratio (OR) = 1.685, < 0.005) and DQB106 (OR = 0.604, = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB105 (OR = 0.764, = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB102 (χ² = 46.475, < 0.001) and DQB106 (χ² = 17.883, < 0.001) and further suggested protective effects of DQB105 (χ² = 16.496, < 0.001). Additionally, the meta-analysis results showed that DRB103 (OR = 2.685, < 0.013), DRB104 (OR = 1.954, < 0.013), and DRB109 (OR = 1.346, < 0.013) are associated with increased LADA risk, while DRB112 (OR = 0.600, < 0.013) and DRB113 (OR = 0.583, < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB103 (χ² = 98.754, < 0.001), DRB104 (χ² = 94.685, < 0.001), DRB109 (χ² = 40.489, < 0.001), DRB101 (χ² = 12.181, < 0.001), DRB107 (χ² = 10.882, = 0.001), and DRB1*08 (χ² = 5.000, = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.
成人隐匿性自身免疫性糖尿病（LADA）最近被证明是成人发病的自身免疫性糖尿病中最常见的形式。病例对照研究已经研究了人类白细胞抗原（HLA）-DQB1 和 HLA-DRB1 多态性与 LADA 风险之间的关系，但它们的结论并不一致。本研究旨在更精确地探讨这些 HLA 基因变异与 LADA 发病之间的相关性。我们系统地检索了包括 PubMed、Embase 和 Medline 在内的 8 个数据库，截至 2018 年 9 月 15 日，检索到相关研究。我们使用荟萃分析和相对易感性效应（RPE）方法进行了这项回顾性研究。荟萃分析结果表明，DQB102（比值比（OR）=1.685， < 0.005）和 DQB106（OR=0.604， = 0.010）对 LADA 的易感性有相反的影响，而 DQB105 导致 LADA 风险显著降低（OR=0.764， = 0.100）在 Bonferroni 校正后消失。RPE 方法证实了 DQB102（χ²=46.475， < 0.001）和 DQB106（χ²=17.883， < 0.001）的作用，并进一步表明 DQB105 具有保护作用（χ²=16.496， < 0.001）。此外，荟萃分析结果显示，DRB103（OR=2.685， < 0.013）、DRB104（OR=1.954， < 0.013）和 DRB109（OR=1.346， < 0.013）与 LADA 风险增加相关，而 DRB112（OR=0.600， < 0.013）和 DRB113（OR=0.583， < 0.013）携带者发生 LADA 的风险降低。此外，RPE 方法揭示了 DRB103（χ²=98.754， < 0.001）、DRB104（χ²=94.685， < 0.001）、DRB109（χ²=40.489， < 0.001）、DRB101（χ²=12.181， < 0.001）、DRB107（χ²=10.882， < 0.001）和 DRB1*08（χ²=5.000， < 0.025）对 LADA 具有保护作用。LADA 与 HLA-DQB1 和 HLA-DRB1 的遗传多态性密切相关，这有助于更好地了解疾病发病机制，并有助于在 LADA 的诊断和治疗中识别易感基因座。
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