- •The first study to examine the combined effects of several SNPs within TLR- 4 on PD risk.
- •The first study to examine the interaction between several SNPs within TLR- 4 and alcohol drinking on PD risk.
- •Independent effects of TLR- 4 single nucleotide polymorphism and PD risk.
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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Published online: December 26, 2018
Accepted: December 11, 2018
Received: April 23, 2018
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