title: Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome.
abstract: Genetic factors are important in the development of metabolic syndrome. However, the genetic background of metabolic syndrome remains unclear. We screened polymorphisms in 85 obesity-related genes to determine which may be associated with metabolic syndrome. A total of 336 single-nucleotide polymorphisms (SNPs) in 85 genes selected from the JSNP database were genotyped. We conducted case-control association analyses using patients with metabolic syndrome (n=1080) and control individuals (n=528) who had no risk of the metabolic syndrome. Three SNPs in the McKusick-Kaufman syndrome (MKKS) gene were significantly related to metabolic syndrome by case-control association study; rs1545 (odds ratio (OR) adjusted for age and gender, 1.45; 95% confidence interval (CI), 1.21-1.74; P=0.000043 (additive model)); rs1547 (OR, 1.45; 95% CI, 1.21-1.74; P=0.000041); and rs2294901 (OR, 1.46; 95% CI, 1.22-1.75; P=0.000033). We selected five tag SNPs (rs2294901, rs221667, rs6133922, rs6077785 and rs6108572) in the MKKS gene. They were in one linkage disequilibrium (LD) block and rs6133922 (P=0.00042), rs6077785 (P=0.000013) and rs6108572 (P=0.000019) as well as rs2294901 were significantly associated with metabolic syndrome. TGAAA haplotype was protective against the metabolic syndrome (P=0.0074), and CCGTT haplotype was susceptible (P=0.00070) to the metabolic syndrome. Our data suggest that genetic variations at MKKS gene influence the risk of metabolic syndrome.
authors.affiliation: Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Kanagawa, Japan. kikuko@src.riken.jp
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Junichi
authors.initials: J
authors.lastname: Takasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakata
authors.forename: Seika
authors.initials: S
authors.lastname: Kamohara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kotani
authors.forename: Ryoya
authors.initials: R
authors.lastname: Komatsu
authors.forename: Naoto
authors.initials: N
authors.lastname: Itoh
authors.forename: Ikuo
authors.initials: I
authors.lastname: Mineo
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hamaguchi
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D056385:Group II Chaperonins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D015203:Reproducibility of Results; D013577:Syndrome
chemical_list: C414726:MKKS protein, human; D056385:Group II Chaperonins