A Common Variant of NGEF Is Associated with Abdominal Visceral Fat in Korean Men.
Central adiposity, rather than body mass index (BMI), is a key pathophysiological feature of the development of obesity-related diseases. Although genetic studies by anthropometric measures such as waist circumference have been widely conducted, genetic studies for abdominal fat deposition measured by computed tomography (CT) have been rarely performed. A total of 1,243 participants who were recruited from two health check-up centers were included in this study. We selected four and three single-nucleotide polymorphisms (SNPs) in NGEF and RGS6, respectively, and analyzed the associations between the seven SNPs and central adiposity measured by CT using an additive, dominant, or recessive model. The participants were generally healthy middle-aged men (50.7 ± 5.3 years). In the additive model, the rs11678490 A allele of NGEF was significantly associated with total adipose tissue, visceral adipose tissue (VAT), and subcutaneous adipose tissue (all P < 0.05). The AA genotype of this SNP in the recessive model showed a more significant association with all adiposity traits, and its association with VAT remained significant even after adjustment for BMI (P = 0.005). In the overall or visceral obesity group analysis, the AA genotype of rs11678490 showed no association with overall obesity (P = 0.148), whereas it was significantly associated with visceral obesity both before (P = 0.010) and after (P = 0.029) adjustment for BMI. In particular, an AA genotype effect was conspicuous between lower and upper groups with 5% extreme VAT phenotypes (OR = 9.59, 95% CI = 1.50-61.31). However, we found no significant association between SNPs of RGS6 and central adiposity. We identified a visceral-fat-associated SNP, rs11678490 of NGEF, in Korean men. This study suggests that the genetic background of central adiposity and BMI is different, and that additional efforts should be made to find the unique genetic architecture of intra-abdominal fat accumulation.
Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, South Korea.
Hyun-Jin
HJ
Kim
Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea.
Jin-Ho
JH
Park
Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, South Korea.
Seungbok
S
Lee
Department of Biochemistry, Seoul National University College of Medicine, Seoul, South Korea.
Ho-Young
HY
Son
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea.
Jinha
J
Hwang
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea.
Jeesoo
J
Chae
Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea.
Jae Moon
JM
Yun
Department of Family Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
Hyuktae
H
Kwon
Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, South Korea; Department of Biochemistry, Seoul National University College of Medicine, Seoul, South Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea.
Jong-Il
JI
Kim
Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea.
Belong
B
Cho
D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D015870:Gene Expression; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D056128:Obesity, Abdominal / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D056910:Republic of Korea; D012307:Risk Factors; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D055105:Waist Circumference
D020662:Guanine Nucleotide Exchange Factors; C504481:NGEF protein, human; D020710:RGS Proteins; C400194:RGS6 protein, human