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* 010401 (OR = 4.51), DQB1*0201 (OR = 2.66) and DQB1*0603 (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*0401 (OR = 0.28), DQA1*0601 (OR = 0.11) and HLA-DQB1*0501 (OR = 0.37) among patients have suggested protective associations. Significant disease associations were observed for two-locus haplotype such as DRB1*13-DQB1*0603 (OR = 11.52), DQA1*01041-DQB1*0603 (OR = 16.50), DQA1*01041-DQB1*0502 (OR = 5.38) and DQA1*0401-DQB1*0603 (OR = 3.027). Protective associations were observed for haplotypes DRB1*10-DQB1*0501 (OR = 0.21), DRB1*15-DQB1*06 (OR = 0.006), DQA1*0401-DQB1*0501 (OR = 0.400) and DQA1*0401-DQB1*0503 (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.