Association between LAG3/CD4 gene variants and risk of Parkinson's disease

Abstract

Background/objectives: Several recent studies suggest a possible role of lymphocyte activation 3 (LAG3) protein. LAG3 can behave as an α-synuclein ligand, and serum and cerebrospinal fluid-soluble LAG3 levels have been proposed as a marker of Parkinson's disease (PD). In this study, we aimed to investigate whether there is an association between 3 common single-nucleotide variations (SNVs) in the LAG3 gene and its closely related CD4 molecule gene and the risk of PD in a Caucasian Spanish population. Two of them have been previously associated with the risk of PD in Chinese females.

Methods: We analysed genotypes and allele frequencies for CD4 rs1922452, CD4 951818 and LAG3 rs870849 SNVs, by using specifically designed TaqMan assays, in a cohort composed of 629 PD patients and 865 age- and gender-matched healthy controls.

Results: The frequencies of the CD4 rs1922452 A/A genotype, according to the dominant and recessive genetic models, and of the CD4 rs1922452/A allelic variant were significantly lower, and the frequencies of the CD4 rs951818 A/A genotype, according to the dominant genetic model, and of the CD4 rs951818/A allele, were significantly higher in PD patients than in controls. The differences were not significant after stratifying by sex. These two SNVs showed strong linkage. Regression models showed a lack of relation between the 3 SNVs studied and the age at onset of PD.

Conclusions: These data suggest a possible role of CD4 rs1922452 and CD4 rs951818 polymorphisms in the risk of PD.

Keywords: CD4 gene; LAG3 gene; Parkinson's disease; genetics; polymorphisms; risk factors.