Diversity and association of HLA/KIR receptors with type 2 diabetes in South India

Abstract

The present study was undertaken to delineate the association(s) of KIR-HLA combination in South Indian Type 2 diabetes mellitus (T2DM) patients. The T2DM patients (n=343) and healthy controls (n=309) were genotyped for KIR/HLA ligands by PCR-SSP method. The increased frequency of activatory KIR (aKIR) 2DS2 (OR=1.91; p<2.91×10-4 ) was observed in patients suggesting a susceptible association. The frequencies of iKIR 2DL2 (OR=0.38; p<1.55×10-5 ) and aKIRs 2DS1 (OR=0.60; p<0.001) and 3DS1 (OR=0.52; p<5.83×10-5 ) were decreased in patients suggesting protective associations. The C1/C2 combinatorial analysis has revealed an increased frequency of C1+ /C2- in T2DM patients (OR=1.62; p<0.014). The KIR "AB" genotype (OR=2.41; p<3.87×10-5 ) was observed to be higher in patients. However, the "BB" genotype (OR=0.32; p<4.71×10-7 ) was increased in controls. The KIR motifs, "Tel-B/B" (OR=1.84; p<0.007), were observed higher among patients. However, the frequency of "Tel-A/B" motif genotype was decreased in patients (OR=0.56; p<3.13×10-4 ). The iKIR/HLA combinations such as 2DL2/3 +C1 and 3DL2+A3/A11 were increased in patients (OR=3.90; p<7.5×10-5 ) suggesting susceptible associations. On the contrary, the aKIR+HLA combinations such as 2DS2+C1, 2DS1+C2 and 3DS1+Bw4 were less frequent in patients (OR=0.32; p<4.2×10-4 ) suggesting protective associations. Thus, the present study clearly establishes the positive and negative associations of different KIR-HLA receptor combinations with T2DM in South India.