Document Type

Article

Publication Date

1-2018

Abstract

The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and is previously associated with neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in the PTPRK with the risk and age at onset (AAO) of Alzheimer’s disease (AD) in 791 AD patients and 782 controls. Five SNPs (top SNP rs4895829 with p=0.0125) were associated with the risk of AD based on a multiple logistic regression (p<0.05); while 6 SNPs (top SNP rs1891150 with p=8.02×10−6) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p=4.65×10−2 and 5.18×10−3, respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p=1.02×10−2) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p=1.39×10−4), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p=4.1×10−3), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p=3.47×10−3), and 8 SNPs associated with total cholesterol (top SNP rs1012049 with p=6.09×10−3). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p=7.3×10−5). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels.

Comments

Publication Title

Journal of psychiatric research

DOI

10.1016/j.jpsychires.2017.09.021

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