Diversity And Association Of Hla/Kir Receptors With Type 2 Diabetes In South India

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 x 10(-4)) was observed in patients suggesting a susceptible association. The frequencies of iKIR 2DL2 (OR = 0.38; p < 1.55 x 10(-5)) and aKIRs 2DS1 (OR = 0.60; p < 0.001) and 3DS1 (OR = 0.52; p < 5.83 x 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 x 10(-5)) was observed to be higher in patients. However, the "BB" genotype (OR = 0.32; p < 4.71 x 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 x 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 x 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 x 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.