title: 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.
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.
authors: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors: Masahiro
authors: M
authors: Nakatochi
authors: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
authors: Yasunori
authors: Y
authors: Ushida
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of CKD Initiatives, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yoshinari
authors: Y
authors: Yasuda
authors: Innovative Research Center for Preventive Medical Engineering, Nagoya University, Nagoya, Japan.
authors: Yasuko
authors: Y
authors: Yoshida
authors: Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors: Shun
authors: S
authors: Kawai
authors: Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors: Ryuji
authors: R
authors: Kato
authors: Safety & Health Promotion Division, Toyota Motor Corporation, Toyota, Japan.
authors: Toru
authors: T
authors: Nakashima
authors: Safety & Health Promotion Division, Toyota Motor Corporation, Toyota, Japan.
authors: Masamitsu
authors: M
authors: Iwata
authors: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors: Yachiyo
authors: Y
authors: Kuwatsuka
authors: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors: Masahiko
authors: M
authors: Ando
authors: Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Nobuyuki
authors: N
authors: Hamajima
authors: Program in Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Takaaki
authors: T
authors: Kondo
authors: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors: Hiroaki
authors: H
authors: Oda
authors: Department of Cardiology, Fujita Health University Second Hospital, Nagoya, Japan.
authors: Mutsuharu
authors: M
authors: Hayashi
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Sawako
authors: S
authors: Kato
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Makoto
authors: M
authors: Yamaguchi
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Shoichi
authors: S
authors: Maruyama
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Seiichi
authors: S
authors: Matsuo
authors: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan; Innovative Research Center for Preventive Medical Engineering, Nagoya University, Nagoya, Japan.
authors: Hiroyuki
authors: H
authors: Honda
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor
references: Blood. 1999 Jun 15;93(12):4277-83
references: 10361125
references: JAMA. 2000 Jan 12;283(2):221-8
references: 10634338
references: J Clin Endocrinol Metab. 2001 May;86(5):1930-5
references: 11344187
references: Diabetologia. 2001 Aug;44(8):946-65
references: 11484071
references: Br J Haematol. 2001 Dec;115(3):701-6
references: 11736957
references: Eur Heart J. 2002 Nov;23(22):1764-70
references: 12419296
references: Metabolism. 2003 Oct;52(10):1246-9
references: 14564674
references: Br J Haematol. 2004 Feb;124(3):343-7
references: 14717782
references: Lancet. 2004 Apr 3;363(9415):1126
references: 15068019
references: J Thromb Haemost. 2006 Jun;4(6):1186-93
references: 16706957
references: Atherosclerosis. 2007 Apr;191(2):298-304
references: 16806226
references: J Am Coll Cardiol. 2007 Jan 30;49(4):403-14
references: 17258085
references: Anal Biochem. 2007 May 1;364(1):78-85
references: 17359929
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: J Lipid Res. 2007 Dec;48(12):2614-21
references: 17768309
references: Lab Hematol. 2008;14(1):1-6
references: 18403313
references: Am J Med. 2008 Sep;121(9):811-9
references: 18724972
references: N Engl J Med. 2008 Nov 20;359(21):2220-32
references: 19020324
references: Diabetes. 2009 Jun;58(6):1403-10
references: 19252134
references: Mol Biol Rep. 2010 Mar;37(3):1513-22
references: 19444646
references: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7
references: 19474294
references: Nat Genet. 2010 Mar;42(3):210-5
references: 20139978
references: Diabetes. 2010 Aug;59(8):2075-9
references: 20460425
references: Bioinformatics. 2010 Sep 1;26(17):2190-1
references: 20616382
references: PLoS One. 2010 Aug 04;5(8):e11961
references: 20694148
references: Diabetes Res Clin Pract. 2011 Jun;92(3):e61-5
references: 21458098
references: Contrib Nephrol. 2011;170:28-35
references: 21659755
references: Obes Rev. 2011 Nov;12(11):952-67
references: 21749608
references: Nature. 2011 Nov 30;480(7376):201-8
references: 22139419
references: Circ Cardiovasc Genet. 2012 Apr 1;5(2):242-9
references: 22399527
references: Nat Genet. 2012 May 13;44(6):659-69
references: 22581228
references: BMC Med Inform Decis Mak. 2012 Aug 01;12:80
references: 22853735
references: Diabetes Metab Syndr. 2012 Jan-Mar;6(1):22-7
references: 23014250
references: Am J Hypertens. 2013 May;26(5):643-56
references: 23443727
references: PLoS One. 2013;8(2):e56216
references: 23468858
references: Endocrine. 2014 Aug;46(3):485-95
references: 24091543
references: BMC Public Health. 2013 Oct 21;13:989
references: 24144016
references: FASEB J. 1993 Feb 1;7(2):308-16
references: 8440408
references: Circulation. 1997 Aug 19;96(4):1102-8
references: 9286936
references: Pharm Res. 1998 Jun;15(6):944-9
references: 9647363