The aim of present study was to elucidate the association of CTLA4 +49 A/G and HLA-DRB1*/DQB1* gene polymorphism in south Indian T1DM patients. The patients and controls (n = 196 each) were enrolled for CTLA4 and HLA-DRB1*/DQB1* genotyping by RFLP/PCR-SSP methods. The increased frequencies of CTLA4 'AG' (OR = 1.99; p = 0.001), 'GG' (OR = 3.94; p = 0.001) genotypes, and 'G' allele (OR = 2.42; p = 9.26 × 10-8) were observed in patients. Reduced frequencies of 'AA' (OR = 0.35; p = 7.19 × 10-7) and 'A' (OR = 0.41; p = 9.26 × 10-8) in patients revealed protective association. Among HLA-DRB1*/DQB1* alleles, DRB1*04 (OR = 3.29; p = 1.0 × 10-5), DRB1*03 (OR = 2.81; p = 1.9 × 10-6), DQB1*02:01 (OR = 2.93; p = 1.65 × 10-5), DQB1*02:02 (OR = 3.38; p = 0.0003), and DQB1*03:02 (OR = 7.72; p = 0.0003) were in susceptible association. Decreased frequencies of alleles, DRB1*15 (OR = 0.32; p = 2.55 × 10-7), DRB1*10 (OR = 0.45; p = 0.002), DQB1*06:01 (OR = 0.43; p = 0.0001), and DQB1*05:02 (OR = 0.28; p = 2.1 × 10-4) in patients were suggested protective association. The combination of DRB1*03+AG (OR = 5.21; p = 1.4 × 10-6), DRB1*04+AG (OR = 2.14; p = 0.053), DRB1*04+GG (OR = 5.21; p = 0.036), DQB1*02:01+AG (OR = 4.44; p = 3.6 × 10-5), DQB1*02:02+AG (OR = 20.9; p = 9.5 × 10-4), and DQB1*02:02+GG (OR = 4.06; p = 0.036) revealed susceptible association. However, the combination of DRB1*10+AA (OR = 0.35; p = 0.003), DRB1*15+AA (OR = 0.22; p = 5.3 × 10-7), DQB1*05:01+AA (OR = 0.45; p = 0.007), DQB1*05:02+AA (OR = 0.17; p = 1.7 × 10-4), DQB1*06:01+AA (OR = 0.40; p = 0.002), and DQB1*06:02+AG (OR = 0.34; p = 0.001) showed decreased frequency in patients, suggesting protective association. In conclusion, CTLA4/HLA-DR/DQ genotypic combinations revealed strong susceptible/protective association toward T1DM in south India. A female preponderance in disease associations was also documented.
Keywords: Autoimmunity; CTLA-4; HLA; PCR-SSP; PCR–RFLP; Polymorphism; T1DM.