Association of a gain-of-function variant in LGR4 with central obesity

Obesity (Silver Spring). 2017 Jan;25(1):252-260. doi: 10.1002/oby.21704. Epub 2016 Dec 7.

Abstract

Objective: To determine the relationship of the gain-of-function variant A750T in leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) with central obesity and related metabolic phenotypes.

Methods: The LGR4 A750T (c.2248 G > A) variant was detected by Sanger sequencing in a discovery young population and a validation community-based population with obesity from eastern China. Fat indices determined by anthropometry and computed tomography scans and clinical biochemical measurements were collected for association analysis.

Results: LGR4 A750T was significantly correlated with waist circumference (P = 0.030) and waist-to-height ratio (P < 0.001) in the young cohort (N = 594) and with waist-to-hip ratio (P = 0.013) in the community population (N = 1067). Combined analysis showed a significant correlation of the variant with waist circumference (P < 0.001) and waist-to-hip ratio (P = 0.021). Moreover, the variant had a remarkable correlation with abdominal visceral fat area (P = 0.004) and was associated with 2-h plasma insulin (P = 0.009) and the Matsuda index (P = 0.027) after an oral glucose tolerance test in young subjects with obesity.

Conclusions: The LGR4 A750T variant may contribute to central obesity characterized by abdominal visceral fat accumulation.

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Mass Index
  • China
  • Cholesterol / blood
  • Genetic Variation*
  • Genotyping Techniques
  • Humans
  • Insulin / blood
  • Insulin Resistance / genetics
  • Intra-Abdominal Fat
  • Linear Models
  • Obesity, Abdominal / epidemiology*
  • Obesity, Abdominal / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Reproducibility of Results
  • Tomography, X-Ray Computed
  • Waist Circumference
  • Waist-Hip Ratio
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • LGR4 protein, human
  • Receptors, G-Protein-Coupled
  • Cholesterol