Abstract

The HLA-DQB1* region exhibits complex associations with autoimmune thyroid disease (AITD). AITD patients (Hashimoto's thyroiditis, HT = 180; Graves' disease, GD = 55) and age/sex matched controls (n = 235) were genotyped for DQB1* alleles by PCR-SSP. Alleles DQB1*02:02, *06:03, *06:09, *03:02, and *03:03 showed an increased risk and *02:01, *05:02, and *06:02 showed a protection toward AITD. Multiple sequence alignment was used to find out the amino acid variations within the peptide-binding pockets of susceptible and/or protective DQB1* alleles. We observed susceptible associations for amino acids 'Glu86(P < 0.0007)' and 'Leu87(P < 3.8 × 10-4)' in P1, 'Leu26(P < 4.0 × 10-12)' in P4, 'His9(P < 5.0 × 10-4)' and 'Ala57(P < 3.6 × 10-4)' in P9 toward HT; and 'Gly86(P < 0.0004)' in P1 and 'Asp57(P < 1.9 × 10-4)' in P9 towards GD. Protective associations were observed for amino acids 'Ala86(P < 8.2 × 10-6)' and 'Tyr87(P < 0.0003)' in P1, 'Gly26(P < 4.9 × 10-5)' and 'Ser74(P < 4.9 × 10-5)' in P4, 'Phe9(P < 0.0007)' and 'Ser57(P < 0.0016)' in P9 towards HT. Thus, the present study revealed that DQB1* alleles and putative amino acid residues play an important role in susceptibility toward AITD in south India.

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