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Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese individuals
  1. Yoshiji Yamada (yamada{at}gene.mie-u.ac.jp)
  1. Life Science Research Center, Mie University, Japan
    1. Kimihiko Kato (p39802{at}govt.pref.gifu.jp)
    1. Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Japan
      1. Tetsuro Yoshida (p41549{at}govt.pref.gifu.jp)
      1. Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Japan
        1. Kiyoshi Yokoi (p88831{at}pref.gifu.lg.jp)
        1. Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Japan
          1. Hitoshi Matsuo (hitomatsuo-circ{at}umin.ac.jp)
          1. Department of Cardiology, Gifu Prefectural General Medical Center, Japan
            1. Sachiro Watanabe (watanabe-sachiro{at}pref.gifu.lg.jp)
            1. Department of Cardiology, Gifu Prefectural General Medical Center, Japan
              1. Norifumi Metoki (n_metoki{at}hirosakistroke-c.jp)
              1. Department of Internal Medicine, Hirosaki Stroke Center, Japan
                1. Hidemi Yoshida (hidemiyo{at}cc.hirosaki-u.ac.jp)
                1. Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Japan
                  1. Kei Satoh (byoutai{at}cc.hirosaki-u.ac.jp)
                  1. Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Japan
                    1. Sahoko Ichihara (saho{at}gene.mie-u.ac.jp)
                    1. Life Science Research Center, Mie University, Japan
                      1. Yukitoshi Aoyagi (aoyagi{at}tmig.or.jp)
                      1. Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Japan
                        1. Akitomo Yasunaga (yasunaga{at}bunka.ac.jp)
                        1. Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Japan
                          1. Hyuntae Park (tonypark{at}p.u-tokyo.ac.jp)
                          1. Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Japan
                            1. Masashi Tanaka (mtanaka{at}tmig.or.jp)
                            1. Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Japan
                              1. Wan Lee (wanlee{at}mail.dongguk.ac.kr)
                              1. Department of Biochemistry, College of Medicine, Dongguk University, Kyungju, Korea, Republic of
                                1. Yoshinori Nozawa (ynozawa{at}giib.or.jp)
                                1. Gifu International Institute of Biotechnology, Japan

                                  Abstract

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

                                  Methods: The study population comprised 2417 unrelated Japanese individuals, including 1522 subjects with metabolic syndrome and 895 controls. The genotypes for 44 polymorphisms of 31 candidate genes related to lipid metabolism were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.

                                  Results: The chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, and smoking status revealed that the -3A→G and 553G→T (Gly185Cys) polymorphisms of APOA5, the 2052T→C (Val653Val) and 1866C→T (Asn591Asn) polymorphisms of LDLR, the 13989A→G (Ile118Val) polymorphism of CYP3A4, and the 1014T→A 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 concentrations of triglycerides and HDL-cholesterol differed significantly (P < 0.05) among APOA5 genotypes; the serum concentration 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 individuals. Genotypes for these polymorphisms may prove informative for prediction of genetic risk for metabolic syndrome.

                                  • APOA5
                                  • C1QTNF5
                                  • CYP3A4
                                  • LDLR
                                  • metabolic syndrome

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