Association of HLA–DRB1, DQA1 and DQB1 alleles and haplotype in Parkinson’s disease from South India

Abstract

Parkinson’s disease (PD) is a chronic, neurodegenerative motor disease exhibiting familial and sporadic forms. The present study was aimed to elucidate the association of HLA-DRB1*, DQA1* and DQB1* alleles with PD. A total of 105 PD patients and 100 healthy controls were typed by PCR-SSP method. We further carried out high-resolution genotyping for DQB1 and DQA1. Results revealed the increased frequencies of alleles DRB1*04 (OR = 2.36), DRB1* 13 (OR = 4.04), DQA1* 01:04:01 (OR = 4.51), DQB1*02:01 (OR = 2.66) and DQB1*06:03 (OR = 2.65) in PD patients suggesting susceptible associations. Further, decreased frequencies observed for alleles DRB1*10 (OR = 0.34), DRB1*15 (OR = 0.44), DQA1*04:01 (OR = 0.28), DQA1*06:01 (OR = 0.11) and HLA-DQB1*05:01 (OR = 0.37) among patients have suggested protective associations. Significant disease associations were observed for two-locus haplotype such as DRB1*13-DQB1*06:03 (OR = 11.52), DQA1*01:041-DQB1*06:03 (OR = 16.50), DQA1*01:041-DQB1*05:02 (OR = 5.38) and DQA1*04:01-DQB1*06:03 (OR = 3.027). Protective associations were observed for haplotypes DRB1*10-DQB1*05:01 (OR = 0.21), DRB1*15-DQB1*06 (OR = 0.006), DQA1*04:01-DQB1*05:01 (OR = 0.400) and DQA1*04:01-DQB1*05:03 (OR = 0.196). The critical amino acid residue analyses have revealed strong susceptible association for the residues of DQB1 alleles such as: L26, S28, K71, T71 and A74, Y9, S30, D37, I37, A38, A57 and S57; and for the residues of DQA1 alleles such as: C11, F61, I74, and M76. Similarly, amino acid residues such as A13, G26, Y26, A71, S74, L9 and V38 of HLA-DQB1 alleles and residues such as Y11, G61, S74 and L76 of DQA1 alleles showed protective associations. Thus, our study documented the susceptible and protective associations of DRB1*, DQB1 and DQA1 alleles and haplotypes in developing the disease and their influence on longevity of PD patients in south India.