A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2

Nat Genet. 1997 Mar;15(3):273-6. doi: 10.1038/ng0397-273.


Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10(-7)). This locus accounted for 47% of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24%. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) and pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / anatomy & histology*
  • Analysis of Variance
  • Arteriosclerosis / genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • Diabetes Mellitus, Type 2 / genetics
  • Family
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Leptin
  • Lod Score
  • Male
  • Obesity / genetics*
  • Pedigree
  • Proteins / metabolism*
  • Risk Factors


  • Genetic Markers
  • Leptin
  • Proteins