Immunogenetic Study of Diabetes Mellitus in Relation to HLA DQ and DR.

INTRODUCTION

Type-1 diabetes mellitus (T1DM) which is also known as insulin-dependent diabetes is diagnosed mainly during childhood and accounts for approximately 5%-10% of all cases of DM. In India, early onset diabetes (<15 years age) constitutes about 1%-4% of the total diabetic population. The insulitis as well as to a humoral (B cell) response with production of antibodies to IAA, GAD, and the protein tyrosine phosphatase IA2 (IA-2AA) is the main pathogenesis of T1DM. Human leukocyte antigen (HLA)-DR and DQ contributes approximately 40%-50% of the inherited susceptibility for T1DM and most frequently involved haplotypes are DRB10301-DQB10201, DRB10301-DQA10501-DQB10201, and DRB10401-DQB1*0302.

METHOD AND MATERIAL

Total 70 cases of DM in age group of 10 years to 65 years and 25 healthy controls of same age group 30 cases of complicated diabetic mellitus were included in the study. 2 mL blood was taken in an EDTA vial for HLA typing and 5 mL blood was taken in a plain vial for anti-GAD antibody. HLA DQB1 and DRB1 were done by sequence specific priming polymerase chain reaction method. Indirect immunofluorescent test was used for anti-GAD antibody. Statistical analysis was performed using SPSS version-16.

RESULTS

Total 40.9% cases of type-I DM were found seropositive for anti-GAD antibody. None of the cases of type-II DM was anti-GAD antibody positive. HLA DRB103010 were significantly more in diabetic patient ( < 0.011) as compared to control. DRB1O403/6 shows that a relative risk of 1.08 was slightly more frequent in DM cases as compared to the control. DQB10201 was significantly high ( < 0.004) in DM patient as compared to control with a relative risk of 1.68. Correlation of DR, DQ antigen with types of DM showed that in type-I DM, DRB103010 was significantly high ( = 0.009) with a relative risk of 2.78 as compared type-II DM. In DQ typing, DQB10201 was significantly high in type-I DM in comparison to type-II DM (65% vs. 30%, = 0.026, RR = 2.05). Comparison of DQB1 in type-I DM with healthy control showed that DQB10201 was significantly high in type-I DM as compared to healthy control ( = 0.0003, RR = 3.09). In type-I DM patient's homozygosity at DRB103010, DRB103010 was significantly high as compared to the control ( < 0.047, RR = 2.33). Correlation of anti-GAD antibody with DRB1 and DQB1 showed that 77.7% anti-GAD antibody positive cases were DRB103010 positive. Similarly, in DQB1 typing, 66.6% anti-GAD positive cases have DQB10201.

CONCLUSION

Prevalence of anti-GAD antibody in Indian population was found up to 45%. HLA DRB13010 and HLA DQB10201 were the most susceptible haplotypes for type-I DM. HLA DRB114 and HLA DRB115 were the protective haplotypes for type-I DM. Susceptibility to type-I DM increases when the homozygosity for DRB1*03010 was present. Diagnosis of type-I DM by anti-GAD antibody was possible in only 40.9% cases but if DRB1 and DQB1 typing is added in the diagnosis then diagnostic efficacy increases up to 83%.