Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population.
There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.
Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Japan. kikuko@src.riken.jp
Kikuko
K
Hotta
Michihiro
M
Nakamura
Takahiro
T
Nakamura
Tomoaki
T
Matsuo
Yoshio
Y
Nakata
Seika
S
Kamohara
Nobuyuki
N
Miyatake
Kazuaki
K
Kotani
Ryoya
R
Komatsu
Naoto
N
Itoh
Ikuo
I
Mineo
Jun
J
Wada
Hiroaki
H
Masuzaki
Masato
M
Yoneda
Atsushi
A
Nakajima
Tohru
T
Funahashi
Shigeru
S
Miyazaki
Katsuto
K
Tokunaga
Manabu
M
Kawamoto
Takato
T
Ueno
Kazuyuki
K
Hamaguchi
Kiyoji
K
Tanaka
Kentaro
K
Yamada
Toshiaki
T
Hanafusa
Shinichi
S
Oikawa
Hironobu
H
Yoshimatsu
Kazuwa
K
Nakao
Toshiie
T
Sakata
Yuji
Y
Matsuzawa
Naoyuki
N
Kamatani
Yusuke
Y
Nakamura
D000328:Adult; D019747:Aldose-Ketose Isomerases / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; C400427:FAIM2 protein, human; C470072:MC4R protein, human; D008565:Membrane Proteins; D044105:Receptor, Melanocortin, Type 4; C443860:SEC16B protein, human; C530715:TMEM18 protein, human; C020582:glucosamine-6-phosphate isomerase; D019747:Aldose-Ketose Isomerases