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 A33 (OR=13.8), A01 (OR=3.69), A02 (OR=2.91), B07 (OR=4.12), DRB111 (OR=2.23), DRB104 (OR=1.51), DRB103 (OR=1.90) and DQB102 (OR=1.49). Protective association was observed for the alleles A11 (OR=0.59), A68 (OR=0.68), B40 (OR=0.50), B54 (OR=0.42), B57 (OR=0.31), B51 (OR=0.29) and DRB110 (OR=0.45). Gender stratified analysis too confirmed many of these associations. Predominant susceptible haplotypes were A33-B40 (OR=10.27), A01-B07 (OR=4.97), A02-B07 (OR=6.50), DRB103-DQB105 (OR=1.88), DRB103-DQB106 (OR=3.01), DRB104-DQB105 (2.63), A01-B07-DRB110 (OR=8.26) and A11-B35-DRB107 (OR=9.338). Haplotypes A03-B07 (OR=0.57; p<0.034) and DRB110-DQB105 (OR=0.57; p<0.033) were protectively associated. Further, a very strong susceptible association was documented for four-locus haplotypes such as A11-B40-DRB115-DQB106 (n=15; OR=16.01; p<0.001); A01-B07-DRB110-DQB105 (n=8; OR=8.26; p<0.043) and A11-B07-DRB107-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.