Objective: The objective of this study was to evaluate the impact of single nucleotide polymorphisms (SNPs) in triggering receptor expressed on the myeloid cells 2 protein (TREM2) gene and their interaction with environmental factors and haplotypes on late-onset Alzheimer's disease (LOAD).
Methods: DNA was extracted from the whole blood of the participants and genotyped using PCR and followed by restriction fragment length polymorphism. The Hardy-Weinberg equilibrium test was used in the control group. Multivariate logistic regression analysis was used to determine the relationship between the 4 SNPs of the TREM2 gene and the risk of LOAD. Generalized multifactor dimensionality reduction was used to test the best interaction combination between SNPs and environmental factors.
Results: Logistic regression analysis showed that the T allele of rs75932628 and the T allele of rs2234253 were independently associated with increased risk of LOAD, and adjusted odds ratios (ORs) were 1.81 (1.271-2.35) and 1.59 (1.15-2.03), respectively. However, there was no significant association with LOAD for rs142232675 and rs143332484. We found a best model significantly associated with LOAD risk that consisted of rs75932628 and smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.012). Stratified analysis indicated that current smokers with rs75932628-CT/TT genotype have the highest LOAD risk compared to never smokers with rs75932628 - CC genotype, OR (95% confidence interval) = 2.73 (1.72-3.79). Haplotypes of rs75932628 and rs2234253 were analyzed using the SHEsis online software. However, no haplotype was found to be significantly associated with the risk of LOAD.
Conclusions: The T allele of rs75932628 and the T allele of rs2234253 and interaction between rs75932628 and smoking were all correlated with increased risk of LOAD.
Keywords: Haplotype; Interaction; Late-onset Alzheimer’s disease; Single nucleotide polymorphisms; TREM2.
© 2021 S. Karger AG, Basel.