Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population.
The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian population are associated with variations in several genes, including neurexin 3 (NRXN3), transcription factor AP-2β (TFAP2B), methionine sulfoxide reductase A (MSRA), lysophospholipase-like-1 (LYPLAL1), fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes. To investigate the relationship between VFA and subcutaneous fat area (SFA) and these genes in the recruited Japanese population, we genotyped 8 single-nucleotide polymorphisms (SNPs) in these 6 genes from 1228 subjects. Multiple regression analysis revealed that gender, age, and rs1558902 and rs1421085 genotypes (additive model) in FTO were significantly associated with body mass index (BMI; P=0.0039 and 0.0039, respectively), SFA (P=0.0027 and 0.0023, respectively) and VFA (P=0.045 and 0.040, respectively). However, SNPs in other genes, namely, NRXN3, TFAP2B, MSRA, LYPLAL1 and MC4R were not significantly associated with BMI, SFA or VFA. Our data suggest that some SNPs, which were identified in genome-wide studies in the Caucasians, also confer susceptibility to fat distribution in the Japanese subjects.
Hotta
Kikuko
K
Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Japan. kikuko@src.riken.jp
Nakamura
Michihiro
M
Nakamura
Takahiro
T
Matsuo
Tomoaki
T
Nakata
Yoshio
Y
Kamohara
Seika
S
Miyatake
Nobuyuki
N
Kotani
Kazuaki
K
Komatsu
Ryoya
R
Itoh
Naoto
N
Mineo
Ikuo
I
Wada
Jun
J
Yoneda
Masato
M
Nakajima
Atsushi
A
Funahashi
Tohru
T
Miyazaki
Shigeru
S
Tokunaga
Katsuto
K
Kawamoto
Manabu
M
Masuzaki
Hiroaki
H
Ueno
Takato
T
Hamaguchi
Kazuyuki
K
Tanaka
Kiyoji
K
Yamada
Kentaro
K
Hanafusa
Toshiaki
T
Oikawa
Shinichi
S
Yoshimatsu
Hironobu
H
Nakao
Kazuwa
K
Sakata
Toshiie
T
Matsuzawa
Yuji
Y
Nakamura
Yusuke
Y
Kamatani
Naoyuki
N
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging*; D008297:Male; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics; D055105:Waist Circumference; D049629:Waist-Hip Ratio
C470072:MC4R protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2; C082354:neurexin IIIalpha; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase