Oncotarget

Clinical Research Papers:

Interaction between PPAR γ and SORL1 gene with Late-Onset Alzheimer’s disease in Chinese Han Population

Hui Zhang, Wei Zheng, Linlin Hua, Yutong Wang, Jinfeng Li, Hongying Bai, Shanshan Wang, Mingyao Du, Xuelian Ma, Chunyang Xu, Xiaodong Li, Bin Gong and Yunliang Wang _

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Oncotarget. 2017; 8:48313-48320. https://doi.org/10.18632/oncotarget.15691

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Abstract

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.


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PII: 15691