title: Association of single-nucleotide polymorphisms in MTMR9 gene with obesity.
abstract: Genetic factors are clearly involved in the development of obesity, but the genetic background of obesity remains largely unclear. Starting from 62 663 gene-based single-nucleotide polymorphisms (SNPs) in three sequential case-control association studies, we identified a replicated association between the obesity phenotype (BMI > or =30 kg/m(2)) and a SNP (rs2293855) located in the myotublarin-related protein 9 (MTMR9) gene in the chromosomal segment 8p23-p22. P-values (minor allele dominant model) of the first set (93 cases versus 649 controls) and the second set (564 cases versus 562 controls) were 0.008 and 0.0002, respectively. The association was replicated in the third set [394 cases versus 958 controls, P = 0.005, odds ratio (95% CI) =1.40 (1.11-1.78)]. The global P-value was 0.0000005. A multiple regression analysis revealed that gender, age BMI and rs2293855 genotype (minor allele dominant model) were significantly associated with both systolic and diastolic blood pressures. MTMR9 was shown to be the only gene within the haplotype block that contained SNPs associated with obesity. Both the transcript and protein of MTMR9 were detected in the rodent lateral hypothalamic area as well as in the arcuate nucleus, and the protein co-existed with orexin, melanin concentrating hormone, neuropeptide Y and proopiomelanocortin. The levels of MTMR9 transcript in the murine hypothalamic region increased after fasting and were decreased by a high-fat diet. Our data suggested that genetic variations in MTMR9 may confer a predisposition towards obesity and hypertension through regulation of hypothalamic neuropeptides.
authors.affiliation: Laboratory for Obesity, SNP Research Center, RIKEN, Kanagawa 230-0045, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yanagiya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanabe
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Susumu
authors.initials: S
authors.lastname: Saito
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sekine
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Seika
authors.initials: S
authors.lastname: Kamohara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakata
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: Shigeru
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
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
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004036:Diet, Atherogenic; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: C435691:MTMR9 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor