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PLoS One. 2015 Feb 3;10(2):e0117591. doi: 10.1371/journal.pone.0117591. eCollection 2015.

Identification of an interaction between VWF rs7965413 and platelet count as a novel risk marker for metabolic syndrome: an extensive search of candidate polymorphisms in a case-control study.

Author information

1
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
2
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
3
Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of CKD Initiatives, Nagoya University Graduate School of Medicine, Nagoya, Japan.
4
Innovative Research Center for Preventive Medical Engineering, Nagoya University, Nagoya, Japan.
5
Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
6
Safety & Health Promotion Division, Toyota Motor Corporation, Toyota, Japan.
7
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
8
Program in Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
9
Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
10
Department of Cardiology, Fujita Health University Second Hospital, Nagoya, Japan.
11
Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
12
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan; Innovative Research Center for Preventive Medical Engineering, Nagoya University, Nagoya, Japan.

Abstract

Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP-SNP interaction, SNP-environment interaction, and SNP-clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS.

PMID:
25646961
PMCID:
PMC4315519
DOI:
10.1371/journal.pone.0117591
[Indexed for MEDLINE]
Free PMC Article

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