Interaction between toll-like receptor 4 (TLR4) gene and alcohol drinking on Parkinson's disease risk in Chinese Han population.

The aim of this study was to investigate the association of several single nucleotide polymorphisms (SNPs) within Toll-like receptor 4 (TLR4) gene, additional SNP- SNP and gene- alcohol drinking interaction with Parkinson's disease (PD) risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 4 SNPs within TLR4 gene and alcohol drinking. Logistic regression was performed to calculate the ORs (95%CI) for association between 4 SNPs within TLR4 gene, additional gene- alcohol drinking interaction and PD risk. PD risk was significantly higher for carriers with the rs7873784- G allele, or with the rs19279149- C allele of within TLR4 gene than those with wild genotypes, adjusted ORs (95%CI) were 0.72 (0.55-0.95) and 0.69 (0.51-0.95). However, we did not find any significant association of rs4986791 and rs11536889 with PD susceptibility after covariates adjustment for age, sex, smoking, alcohol drinking and BMI. GMDR analysis indicated a significant two-locus model (p = 0.0010) involving rs1927914 and alcohol drinking, the cross-validation consistency of the two- locus models was 10/ 10, and the testing accuracy was 60.11%. In logistic regression analysis, we found that never alcohol- drinkers with rs1927914- TC or CC genotype within TLR4 gene have the lowest PD risk, compared to drinkers with rs1927914- TT genotype, OR (95%CI) = 0.42 (0.28-0.61), after covariates adjustment. The rs7873784- G and rs19279149- C allele within TLR4 gene, interaction between rs1927914 and alcohol drinking were associated with decreased PD risk.

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