Variations in the FTO gene are associated with severe obesity in the Japanese.
Variations in the fat-mass and obesity-associated gene (FTO) are associated with the obesity phenotype in many Caucasian populations. This association with the obesity phenotype is not clear in the Japanese. To investigate the relationship between the FTO gene and obesity in the Japanese, we genotyped single nucleotide polymorphisms (SNPs) in the FTO genes from severely obese subjects [n = 927, body mass index (BMI) > or = 30 kg/m2] and normal-weight control subjects (n = 1,527, BMI < 25 kg/m2). A case-control association analysis revealed that 15 SNPs, including rs9939609 and rs1121980, in a linkage disequilibrium (LD) block of approximately 50 kb demonstrated significant associations with obesity; rs1558902 was most significantly associated with obesity. P value in additive mode was 0.0000041, and odds ratio (OR) adjusted for age and gender was 1.41 [95% confidential interval (CI) = 1.22-1.62]. Obesity-associated phenotypes, which include the level of plasma glucose, hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and blood pressure were not associated with the rs1558902 genotype. Thus, the SNPs in the FTO gene were found to be associated with obesity, i.e., severe obesity, in the Japanese.
Hotta
Kikuko
K
Laboratory for Obesity, SNP Research Center, RIKEN, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. kikuko@src.riken.jp.
Nakata
Yoshio
Y
Institute of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan.
Matsuo
Tomoaki
T
Institute of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan.
Kamohara
Seika
S
Medicine and Health Science Institute, Tokyo Medical University, Tokyo, Japan.
Kotani
Kazuaki
K
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Komatsu
Ryoya
R
Rinku General Medical Center, Osaka, Japan.
Itoh
Naoto
N
Toyonaka Municipal Hospital, Osaka, Japan.
Mineo
Ikuo
I
Otemae Hospital, Osaka, Japan.
Wada
Jun
J
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Masuzaki
Hiroaki
H
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yoneda
Masato
M
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Nakajima
Atsushi
A
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Miyazaki
Shigeru
S
Tokyo Postal Services Agency Hospital, Tokyo, Japan.
Tokunaga
Katsuto
K
Itami City Hospital, Hyogo, Japan.
Kawamoto
Manabu
M
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Funahashi
Tohru
T
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hamaguchi
Kazuyuki
K
Department of Community Health and Gerontological Nursing, Faculty of Medicine, Oita University, Oita, Japan.
Yamada
Kentaro
K
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University, Fukuoka, Japan.
Hanafusa
Toshiaki
T
First Department of Internal Medicine, Osaka Medical College, Osaka, Japan.
Oikawa
Shinichi
S
Division of Endocrinology and Metabolism, Department of Medicine, Nippon Medical School, Tokyo, Japan.
Yoshimatsu
Hironobu
H
Department of Anatomy, Biology and Medicine, Faculty of Medicine, Oita University, Oita, Japan.
Nakao
Kazuwa
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Sakata
Toshiie
T
Department of Anatomy, Biology and Medicine, Faculty of Medicine, Oita University, Oita, Japan.
Matsuzawa
Yuji
Y
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Tanaka
Kiyoji
K
Institute of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan.
Kamatani
Naoyuki
N
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.|Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo, Japan.
Nakamura
Yusuke
Y
Laboratory for Molecular Medicine, Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human