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

Abstract

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