Critical amino acid variations in HLA-DQB1* molecules confers susceptibility to Autoimmune Thyroid Disease in south India

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 ‘Glu 86 ( P < 0.0007)’ and ‘Leu 87 ( P < 3.8 × 10 −4 )’ in P1, ‘Leu 26 ( P < 4.0 × 10 −12 )’ in P4, ‘His 9 ( P < 5.0 × 10 −4 )’ and ‘Ala 57 ( P < 3.6 × 10 −4 )’ in P9 toward HT; and ‘Gly 86 ( P < 0.0004)’ in P1 and ‘Asp 57 ( P < 1.9 × 10 −4 )’ in P9 towards GD. Protective associations were observed for amino acids ‘Ala 86 ( P < 8.2 × 10 −6 )’ and ‘Tyr 87 ( P < 0.0003)’ in P1, ‘Gly 26 ( P < 4.9 × 10 −5 )’ and ‘Ser 74 ( P < 4.9 × 10 −5 )’ in P4, ‘Phe 9 ( P < 0.0007)’ and ‘Ser 57 ( 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.