Clinical Research Papers:
Interaction between PPAR γ and SORL1 gene with LateOnset Alzheimer’s disease in Chinese Han Population
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Hui Zhang1,*, Wei Zheng2,*, Linlin Hua2, Yutong Wang3, Jinfeng Li1, Hongying Bai4, Shanshan Wang1, Mingyao Du1, Xuelian Ma1, Chunyang Xu4, Xiaodong Li4, Bin Gong1 and Yunliang Wang4,1
1 Department of Neurology, The 148 Central Hospital of PLA, Shandong, China
2 The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3 Medical College of Henan University, Kaifeng, China
4 Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
* These authors have contributed equally to this work
Correspondence: to
Yunliang Wang, email:
Bin Gong, email:
Keywords: SORL1; PPAR G; single nucleotide polymorphism; alcohol drinking; interaction
Received: January 10, 2017 Accepted: February 12, 2017 Published: February 25, 2017
Abstract
Aims: To investigate the impact of sortilin-related receptor 1 gene 1 (SORL1) and peroxisome proliferator activated receptor gamma (PPAR G) gene single nucleotide polymorphisms (SNPs), gene- gene and gene- environment interactions and haplotype on late-onset Alzheimer’s disease (LOAD) risk.
Methods: Hardy-Weinberg equilibrium (HWE), haplotype analysis and pairwise linkage disequilibrium (LD) analysis were investigated by using SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats). Logistic regression was performed to investigate association between SNPs and LOAD. Generalized multifactor dimensionality reduction (GMDR) was used to investigate the interaction among gene- gene and gene- environment interaction.
Results: Logistic regression analysis showed that LOAD risk was significantly higher in carriers of the A allele of rs1784933 polymorphism than those with GG (GA+ AA versus GG), adjusted OR (95%CI) = 1.63(1.27-1.98), and higher in carriers of G allele of the rs1805192 polymorphism than those with CC (CG+ GG versus CC), adjusted OR (95%CI) = 1.70 (1.25-2.27). GMDR analysis suggested a significant two-locus model (p = 0.0010) involving rs1784933 and rs1805192, and a significant two-locus model (p = 0.0100) involving rs1784933 and alcohol drinking. Haplotype containing the rs1784933- A and rs689021- C alleles were associated with a statistically increased LOAD risk (OR = 1.86, 95%CI = 1.37– 2.52, p < 0.001).
Conclusions: We conclude that rs1784933 and rs1805192 minor alleles, gene- gene interaction between rs1784933 and rs1805192, gene- environment interaction between rs1784933 and alcohol drinking, and haplotype containing the rs1784933- A and rs689021- C alleles are all associated with increased LOAD risk.