A Common Variant of NGEF Is Associated with Abdominal Visceral Fat in Korean Men

PLoS One. 2015 Sep 4;10(9):e0137564. doi: 10.1371/journal.pone.0137564. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Body Mass Index
  • Case-Control Studies
  • Gene Expression
  • Genotype
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Intra-Abdominal Fat / diagnostic imaging
  • Intra-Abdominal Fat / metabolism*
  • Intra-Abdominal Fat / physiopathology
  • Male
  • Middle Aged
  • Models, Genetic
  • Obesity, Abdominal / diagnostic imaging
  • Obesity, Abdominal / genetics
  • Obesity, Abdominal / metabolism*
  • Obesity, Abdominal / physiopathology
  • Polymorphism, Single Nucleotide*
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism
  • Republic of Korea
  • Risk Factors
  • Sex Factors
  • Subcutaneous Fat / diagnostic imaging
  • Subcutaneous Fat / metabolism*
  • Subcutaneous Fat / physiopathology
  • Tomography, X-Ray Computed
  • Waist Circumference

Substances

  • Guanine Nucleotide Exchange Factors
  • NGEF protein, human
  • RGS Proteins
  • RGS6 protein, human

Grants and funding

This research was supported by iPET (Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (Grant No. 113032032HD020) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2012R1A5A2A44671346).