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.
基金:
National Natural Science Foundation of China [81400782, 81170725, 81400783]; Key Research and Development Program of Hunan Province Science and Technology Project [2015JC3020]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1195]; National Key Technology Research and Development Program [2012BAI02B04, 2013BAI09B12]; Research Fund for the Doctoral Program of Higher Education of China [20120162110044]
第一作者单位:[1]Cent S Univ, Xiangya Hosp 2, Dept Endocrinol & Metab, Changsha 410011, Hunan, Peoples R China[2]Cent S Univ, Ctr Diabet, Dept Endocrinol & Metab, Inst Metab & Endocrinol, Changsha 410011, Hunan, Peoples R China[3]Minist Educ, Natl Clin Res Ctr Metab Dis, Key Lab Diabet Immunol, Changsha 410011, Hunan, Peoples R China
通讯作者:
通讯机构:[1]Cent S Univ, Xiangya Hosp 2, Dept Endocrinol & Metab, Changsha 410011, Hunan, Peoples R China[2]Cent S Univ, Ctr Diabet, Dept Endocrinol & Metab, Inst Metab & Endocrinol, Changsha 410011, Hunan, Peoples R China[3]Minist Educ, Natl Clin Res Ctr Metab Dis, Key Lab Diabet Immunol, Changsha 410011, Hunan, Peoples R China[6]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Ctr Biomed Res, 1095 Jiefang Ave, Wuhan 430030, Hunan, Peoples R China[*1]Minist Educ, Key Lab Diabet Immunol, Changsha 410011, Hunan, Peoples R China[*2]Natl Clin Res Ctr Metab Dis, Changsha 410011, Hunan, Peoples R China
推荐引用方式(GB/T 7714):
Luo Shuoming,Lin Jian,Xie Zhiguo,et al.HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6[J].JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM.2016,101(4):1693-1700.doi:10.1210/jc.2015-3771.
APA:
Luo, Shuoming,Lin, Jian,Xie, Zhiguo,Xiang, Yufei,Zheng, Peilin...&Zhou, Zhiguang.(2016).HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,101,(4)
MLA:
Luo, Shuoming,et al."HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 101..4(2016):1693-1700