Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients
The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between β-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North...
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| Format: | Article |
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Wiley
2021-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2021/4012893 |
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| author | Neihenuo Chuzho Neeraj Kumar Neetu Mishra Nikhil Tandon Uma Kanga Gurvinder Kaur Paras Singh Gunja Mishra Shreya Sharma Narinder K. Mehra |
| author_facet | Neihenuo Chuzho Neeraj Kumar Neetu Mishra Nikhil Tandon Uma Kanga Gurvinder Kaur Paras Singh Gunja Mishra Shreya Sharma Narinder K. Mehra |
| author_sort | Neihenuo Chuzho |
| collection | DOAJ |
| description | The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between β-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North India and investigated the genetic association of GADA and IA2A with HLA class I and class II genes/haplotypes. GADA and IA2A were detected in 50.79% and 15.87% of T1D patients, respectively, while only 8.73% had both GADA and IA2A. HLA-DRB1∗03 was observed to be significantly higher in GADA+ T1D patients as compared to GADA– (91.41% vs. 66.13%, Bonferroni-corrected P Pc=1.11×10−5; OR=5.45; 95% CI: 2.67-11.08). Similarly, HLA-DQB1∗02 was found to be significantly increased in GADA+ patients (94.53%, Pc=2.19×10−5; OR=6.27; 95% CI: 2.7-14.49) as compared to GADA– (73.39%). The frequencies of HLA-DRB1∗04 and DQB1∗03 were increased in IA2A+ patients (45.0% and 52.5%, respectively) as compared to that in IA2A– (25.94% and 33.96%, respectively). Further, the frequency of DRB1∗03-DQB1∗02 haplotype was found to be significantly increased in GADA+ T1D patients as compared to GADA- (60.55% vs. 41.94%, P=3.94×10−5; OR=2.13; 95%CI=1.49-3.03). Similarly, HLA-DRB1∗04-DQB1∗03 haplotype was found to be significantly increased in IA2A+ T1D patients compared to IA2A– patients (22.5% vs. 12.97%; P=0.041; OR=1.95; 95%CI=1.08-3.52). None of the HLA class I genes (HLA-A, B, and Cw) was found to be associated with GADA or IA2A in people with T1D. Our findings suggest that HLA-DRB1∗03/DQB1∗02 and HLA-DRB1∗04/DQB1∗03 might play an important role in the development of GADA and IA2A, respectively. |
| format | Article |
| id | doaj-art-fc66333f8c094f01a6f66e083c26bf8f |
| institution | Kabale University |
| issn | 2314-6753 |
| language | English |
| publishDate | 2021-01-01 |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-fc66333f8c094f01a6f66e083c26bf8f2025-02-03T01:04:16ZengWileyJournal of Diabetes Research2314-67532021-01-01202110.1155/2021/4012893Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes PatientsNeihenuo Chuzho0Neeraj Kumar1Neetu Mishra2Nikhil Tandon3Uma Kanga4Gurvinder Kaur5Paras Singh6Gunja Mishra7Shreya Sharma8Narinder K. Mehra9Indian Council of Medical Research (ICMR)-National Institute of PathologyIndian Council of Medical Research (ICMR)-National Institute of PathologySymbiosis School of Biological SciencesDepartment of Endocrinology and MetabolismDepartment of Transplant Immunology and ImmunogeneticsLaboratory Oncology UnitDepartment of Molecular MedicineIndian Council of Medical Research (ICMR)-National Institute of PathologyDepartment of Endocrinology and MetabolismEmeritus Scientist (ICMR), and Former Dean (Research)The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between β-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North India and investigated the genetic association of GADA and IA2A with HLA class I and class II genes/haplotypes. GADA and IA2A were detected in 50.79% and 15.87% of T1D patients, respectively, while only 8.73% had both GADA and IA2A. HLA-DRB1∗03 was observed to be significantly higher in GADA+ T1D patients as compared to GADA– (91.41% vs. 66.13%, Bonferroni-corrected P Pc=1.11×10−5; OR=5.45; 95% CI: 2.67-11.08). Similarly, HLA-DQB1∗02 was found to be significantly increased in GADA+ patients (94.53%, Pc=2.19×10−5; OR=6.27; 95% CI: 2.7-14.49) as compared to GADA– (73.39%). The frequencies of HLA-DRB1∗04 and DQB1∗03 were increased in IA2A+ patients (45.0% and 52.5%, respectively) as compared to that in IA2A– (25.94% and 33.96%, respectively). Further, the frequency of DRB1∗03-DQB1∗02 haplotype was found to be significantly increased in GADA+ T1D patients as compared to GADA- (60.55% vs. 41.94%, P=3.94×10−5; OR=2.13; 95%CI=1.49-3.03). Similarly, HLA-DRB1∗04-DQB1∗03 haplotype was found to be significantly increased in IA2A+ T1D patients compared to IA2A– patients (22.5% vs. 12.97%; P=0.041; OR=1.95; 95%CI=1.08-3.52). None of the HLA class I genes (HLA-A, B, and Cw) was found to be associated with GADA or IA2A in people with T1D. Our findings suggest that HLA-DRB1∗03/DQB1∗02 and HLA-DRB1∗04/DQB1∗03 might play an important role in the development of GADA and IA2A, respectively.http://dx.doi.org/10.1155/2021/4012893 |
| spellingShingle | Neihenuo Chuzho Neeraj Kumar Neetu Mishra Nikhil Tandon Uma Kanga Gurvinder Kaur Paras Singh Gunja Mishra Shreya Sharma Narinder K. Mehra Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients Journal of Diabetes Research |
| title | Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients |
| title_full | Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients |
| title_fullStr | Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients |
| title_full_unstemmed | Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients |
| title_short | Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients |
| title_sort | differential hla association of gad65 and ia2 autoantibodies in north indian type 1 diabetes patients |
| url | http://dx.doi.org/10.1155/2021/4012893 |
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