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Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people

¹ Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan
² Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
³ Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Japan
⁴ Department of Internal Medicine, Hirosaki Stroke Center, Hirosaki, Japan
⁵ Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan
⁶ Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
⁷ Department of Biochemistry, College of Medicine, Dongguk University, Kyungju, Korea
⁸ Gifu International Institute of Biotechnology, Kakamigahara, Japan

Correspondence to:
Yoshiji Yamada, MD, PhD, FAHA, Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan; yamada{at}gene.mie-u.ac.jp]

Background: The aetiology of metabolic syndrome is complex, being determined by the interplay of both genetic and environmental factors. The aim of this study was to identify genetic polymorphisms that confer susceptibility to metabolic syndrome, to allow prediction of genetic risk for this condition.

Methods: The study population comprised 2417 unrelated Japanese subjects (1522 with metabolic syndrome and 895 controls). The genotypes for 44 polymorphisms of 31 candidate genes related to lipid metabolism were determined using a combination of PCR and sequence-specific oligonucleotide probes with suspension array technology.

Results: The ² test and subsequent multivariate logistic regression analysis with adjustment for age, sex and smoking status found that the–3AG and 553GT (Gly185Cys) polymorphisms of APOA5, the 2052TC (Val653Val) and 1866CT (Asn591Asn) polymorphisms of LDLR, the 13989AG (Ile118Val) polymorphism of CYP3A4 and the 1014TA polymorphism of C1QTNF5 were significantly (false discovery rate <0.05) associated with the prevalence of metabolic syndrome, with the variant alleles of APOA5 and C1QTNF5 representing risk factors for and those of LDLR and CYP3A4 being protective against this condition. Serum levels of triglycerides and high-density lipoprotein (HDL) cholesterol differed significantly (p<0.05) among APOA5 genotypes; the serum level of HDL cholesterol differed among LDLR genotypes; and the fasting plasma glucose level and body mass index differed between CYP3A4 and C1QTNF5 genotypes, respectively.

Conclusions: APOA5, LDLR, CYP3A4 and C1QTNF5 are susceptibility loci for metabolic syndrome in Japanese people. Genotypes for these polymorphisms may prove informative for prediction of genetic risk for metabolic syndrome.