Association of HLA-A, B, DRB1* and DQB1* alleles and haplotypes in south Indian T2DM patients.

The genes of Human Leukocyte Antigen (HLA) system are implicated in the susceptibility of several diseases including Type 2 diabetes (T2DM). Therefore, we aimed to investigate the association of HLA alleles with T2DM in south India. A total of 344 patients (195 males; 149 females) and 309 controls (186 males; 123 females) were genotyped for HLA-DR/-DQ alleles. Based on predominant DR/DQ haplotypes, 222 patients and 222 age/sex matched controls were HLA-A/-B genotyped. HLA alleles were typed by PCR-SSP methods. Susceptible association was observed for the alleles A*33 (OR=13.8), A*01 (OR=3.69), A*02 (OR=2.91), B*07 (OR=4.12), DRB1*11 (OR=2.23), DRB1*04 (OR=1.51), DRB1*03 (OR=1.90) and DQB1*02 (OR=1.49). Protective association was observed for the alleles A*11 (OR=0.59), A*68 (OR=0.68), B*40 (OR=0.50), B*54 (OR=0.42), B*57 (OR=0.31), B*51 (OR=0.29) and DRB1*10 (OR=0.45). Gender stratified analysis too confirmed many of these associations. Predominant susceptible haplotypes were A*33-B*40 (OR=10.27), A*01-B*07 (OR=4.97), A*02-B*07 (OR=6.50), DRB1*03-DQB1*05 (OR=1.88), DRB1*03-DQB1*06 (OR=3.01), DRB1*04-DQB1*05 (2.63), A*01-B*07-DRB1*10 (OR=8.26) and A*11-B*35-DRB1*07 (OR=9.338). Haplotypes A*03-B*07 (OR=0.57; p<0.034) and DRB1*10-DQB1*05 (OR=0.57; p<0.033) were protectively associated. Further, a very strong susceptible association was documented for four-locus haplotypes such as A*11-B*40-DRB1*15-DQB1*06 (n=15; OR=16.01; p<0.001); A*01-B*07-DRB1*10-DQB1*05 (n=8; OR=8.26; p<0.043) and A*11-B*07-DRB1*07-DQB1*05 (n=8; OR=8.26; p<0.043). Thus, a number of HLA alleles and haplotypes showed susceptible and protective association(s) in T2DM patients from south India.