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Immunogenetic study of diabetes mellitus in relation to HLA DQ and DR and to find out the prevalence of anti-GAD and anti-islet antibody

Gyanendra Singh and Usha

Introduction: In India, early onset diabetes constitutes about 1%–4% of the total diabetic population. The insulitis as well as humoral B-cell response with production of antibodies to IAA, GAD and the protein tyrosine phosphatase IA2 is the main pathogenesis of T1DM. HLA-DR and DQ contributes approximately 40%–50% of the inherited susceptibility for T1DM and most frequently involved haplotypes are DRB1*0301‑DQB1*0201, DRB1*0301‑DQA1*0501. Method and Material: The study included 70 cases of DM, 25 healthy controls and 30 cases of complicated DM. HLA- DQB1 and DRB1 were done by sequence specific PCR method. Indirect immunofluorescent test was used for anti‑GAD antibody. Statistical analysis done by SPSS version‑16. Results: HLA DRB1*03010 were significantly more in diabetic patient (P < 0.011) as compared to control. DRB1*O403/6 and DQB1*0201 (p value <0.004) was significantly high in DM patient as compared to control with a relative risk of 1.08 and 1.68 respectively. In type‑I DM, DRB1*03010 was significantly high (P = 0.009) with a relative risk of 2.78 as compared type‑II DM. In DQ typing, DQB1*0201 was significantly high in type‑I DM in comparison to type‑II DM (65% vs. 30%, P = 0.026, RR = 2.05). DQB1*0201 was significantly high in type‑I DM as compared to healthy control (P = 0.0003, RR = 3.09). In type‑I DM patient’s homozygosity at DRB1*03010, DRB1*03010 was significantly high as compared to the control (P < 0.047, RR = 2.33). DRB1*03010 was positive in 77.7% anti‑GAD antibody positive cases. Similarly, in DQB1 typing, 66.6% anti‑GAD positive cases have DQB1*0201. Conclusion: HLA DRB1*3010 and HLA DQB1*0201 were the most susceptible and HLA DRB1*14 and HLA DRB1*15 were the protective haplotypes for type‑I DM. Susceptibility increases for homozygosity for DRB1*03010. Diagnostic efficacy for T1 DM increase from 40.9% to 83% if DRB1 and DQB1 typing is added with anti‑GAD antibody.