HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6
HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6
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成人潜伏性自身免疫性糖尿病与 1 型糖尿病之间的 HLA 遗传差异：LADA 中国研究第 6 号
DOI：
10.1210/jc.2015-3771
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发表时间：
2016-04-01
影响因子：
5.8
通讯作者：
Zhou, Zhiguang
中科院分区：
文献类型：
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作者：
Luo, Shuoming;Lin, Jian;Zhou, Zhiguang
内容：人类白细胞抗原（HLA）-DRB 1-DQA 1-DQB 1方面的差异赋予成人隐匿性自身免疫性糖尿病（LADA）和1型糖尿病（T1 D）患者之间的风险仍然几乎完全未知。本研究的目的是确定和比较LADA和T1D.Design之间的HLA赋予的风险：病例对照研究进行了一个具有代表性的中国数据集，包括520例T1 D患者，562例LADA患者和1065名对照。分析HLA易感单倍型和基因型的频率和比值比，以及DQ-α链中第52位残基精氨酸或DQ-α链中第57位残基天冬氨酸的频率和比值比。DRB 1 *0405-DQA 1 *03-DQB 1 *0401和DRB 1 *0901-DQA 1 *03-DQB 1 *0303是LADA的主要易感单倍型，这也赋予了T1 D相似的风险（比值比分别为2.02 vs 2.20和1.61 vs 2.30）。强相关的T1 D单倍型DRB 1 *0301-DQA 1 *05-DQB 1 *0201也与LADA相关，但仅赋予一半的T1 D风险（比值比2.65 vs 4.84）。有趣的是，最易感的T1 D单倍型DRB 1 *0901-DQA 1 *05-DQB 1 *0201、DRB 1 *0301-DQA 1 *03-DQB 1 *0201和DRB 1 *0301-DQA 1 *03-DQB 1 *0303与LADA无关。DR 3/DR 3、DR 3/DR 9和DR 9/DR 9基因型与T1 D易感性高度相关，而只有DR 9/DR 9赋予LADA风险。DR 3/DR 3是中国T1 D患者的高危基因型，其表现出与白人DR 3/DR 4基因型相似的风险，但频率较低。DR 9/DR 9是中国人LADA的高危基因型。结论：HLA-DRB 1-DQA 1-DQB 1基因座对LADA的易感性与T1 D的易感性有显著差异，DQ-α精氨酸52位阳性、DQ-α天冬氨酸57位阴性的等位基因及其顺式或反式组合对LADA的易感性无显著差异。这一信息将有助于对亚洲LADA患者进行分类，这也将为了解其病因提供新的见解。
Context: The discrepancies in terms of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 conferred risks between latent autoimmune diabetes in adults (LADA) and type 1 diabetes (T1D) patients remained almost completely unknown. The goal of the current study is to determine and compare HLA-conferred risks between LADA and T1D.Design: A case-control study was conducted in a representative Chinese data set containing 520 T1D patients, 562 LADA patients, and 1065 controls. The frequencies and odds ratios for HLA susceptible haplotypes and genotypes and for arginine at residue 52 in the DQ-alpha chain or aspartic acid at residue 57 in the DQ-alpha chain were analyzed.Results: DRB1*0405-DQA1*03-DQB1*0401 and DRB1*0901-DQA1*03-DQB1*0303 are the major LADA susceptible haplotypes, which also confer comparable risks for T1D (odds ratio 2.02 vs 2.20 and 1.61 vs 2.30, respectively). The strongly associated T1D haplotype DRB1*0301-DQA1*05-DQB1*0201 is also associated with LADA but confers only half of the T1D risk (odds ratio 2.65 vs 4.84). Interestingly, the most susceptible T1D haplotypes, DRB1*0901-DQA1*05-DQB1*0201, DRB1*0301-DQA1*03-DQB1*0201, and DRB1*0301-DQA1*03-DQB1*0303, are not associated with LADA. Genotypes for DR3/DR3, DR3/DR9, and DR9/DR9 are highly associated with T1D susceptibility, whereas only DR9/DR9 confers risk for LADA. DR3/DR3 is the high-risk genotype in Chinese T1D patients, which manifests similar risk as the DR3/DR4 genotype in Caucasians but with a lower frequency. DR9/DR9 is the high risk LADA genotype in Chinese. Alleles with DQ-alpha arginine at residue 52-positive, DQ-alpha aspartic acid at residue 57-negative, and their combination formed in cis or trans confer susceptibility to T1D but not to LADA.Conclusion: Our results suggest that LADA risk conferred by HLA-DRB1-DQA1-DQB1 loci in Chinese differs significantly from that of T1D risk. This information would be useful for classifying Asian LADA patients, which should provides novel insight into the understanding of its pathoetiology as well.