Genetic variations in the leptin and leptin receptor genes are associated with type 2 diabetes mellitus and metabolic traits in the Korean female population

Clin Genet. 2008 Aug;74(2):105-15. doi: 10.1111/j.1399-0004.2008.01033.x. Epub 2008 Jun 28.

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). We observed reproducibility of these results using the KHGS data; LEP+4950G>A and +4998A>C were significantly associated with systolic blood pressure and low-density lipoprotein cholesterol level, respectively. In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics
  • Blood Pressure
  • Body Mass Index
  • Case-Control Studies
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Humans
  • Korea / epidemiology
  • Leptin / genetics*
  • Metabolism / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Leptin / genetics*

Substances

  • Cholesterol, LDL
  • Leptin
  • Receptors, Leptin