Identification of an Interaction between <i>VWF</i> rs7965413 and Platelet Count as a Novel Risk Marker for Metabolic Syndrome: An Extensive Search of Candidate Polymorphisms in a Case-Control Study

<div><p>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 (<i>P</i> < 0.05): <i>LRP2</i> rs2544390, rs1800592 between <i>UCP1</i> and <i>TBC1D9</i>, <i>APOA5</i> rs662799, <i>VWF</i> rs7965413, and rs1411766 between <i>MYO16</i> and <i>IRS2</i>. 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, <i>P</i> = 0.004; SNP × CP interaction term: OR = 1.33, <i>P</i> = 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.</p></div

Age-adjusted ORs for MetS in platelet ≥ 23.8×10⁴/μL and < 23.8×10⁴/μL with different rs7965413 genotypes The vertical bars represent the 95% CIs.

<p>The horizontal dashed line indicates the null value (odds ratio (OR) = 1.0). OR represents risk of MetS development in the group with each genotype of rs7965413 and each dichotomous platelet count compared with the group with the CC genotype and PLT count of < 23.8×10⁴/μL. *: <i>P</i> < 0.05.</p