title: Association of genetic variants with dyslipidemia.
abstract: Although genetic variants, which regulate lipid metabolism, have been extensively investigated in Caucasian populations, the genes, which confer susceptibility to dyslipidemia in Japanese individuals, remain to be elucidated. The aim of the present study was to examine a possible association among hypertriglyceridemia, hypo‑high density lipoprotein (HDL)‑cholesterolemia or hyper‑low density lipoprotein (LDL)‑cholesterolemia in Japanese individuals with 29 polymorphisms observed to confer susceptibility for coronary heart disease. This was performed through meta‑analyses of genome‑wide association studies in Caucasian populations. The study population comprised 2,354 individuals with dyslipidemia (hypertriglyceridemia, hypo‑HDL‑cholesterolemia or hyper‑LDL‑cholesterolemia) and 3,106 control individuals. To compensate for multiple comparisons of genotypes, a false discovery rate (FDR) of <0.05 was adopted to determine the statistical significance of the associations. Comparisons of allele frequencies using the χ2 test revealed that rs964184 of zinc finger gene (ZPR1; FDR=2.1x10‑7), rs4845625 of interleukin 6 receptor (IL6R; FDR=0.032), rs46522 of ubiquitin‑conjugating enzyme E2Z gene (UBE2Z; FDR=0.032) and rs17514846 of furin (FDR=0.041) were significantly associated with hypertriglyceridemia. The χ2 test revealed that rs599839 of proline/serine‑rich coiled‑coil 1 (PSRC1; FDR=0.004) and rs2075650 of translocase of outer mitochondrial membrane 40 homolog (TOMM40; FDR=0.004) were significantly associated with hyper‑LDL‑cholesterolemia. Multivariate logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 (P=5.1x10‑7; odds ratio, 1.37; dominant model), rs4845625 of IL6R (P=0.0019, odds ratio, 1.25; dominant model) and rs46522 of UBE2Z (P=0.0039, odds ratio, 1.19; dominant model) were significantly associated with hypertriglyceridemia, and that rs599839 of PSRC1 (P=0.0004, odds ratio, 0.70; dominant model) and rs2075650 of TOMM40 (P=0.0004, odds ratio, 1.43; dominant model) were significantly associated with hyper‑LDL‑cholesterolemia. Therefore, ZPR1, IL6R, and UBE2Z may be susceptibility loci for hypertriglyceridemia, whereas PSRC1 and TOMM40 may be such loci for hyper-LDL-cholesterolemia in Japanese individuals.
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500‑8717, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500‑8717, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Tokoro
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500‑8717, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsuoka
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500‑8717, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500‑8717, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500‑8717, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507‑8522, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511‑0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.affiliation: Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi 453‑8511, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465‑0025, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514‑8507, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D015415:Biomarkers; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D014280:Triglycerides