A Major Quantitative Trait Locus Determining Serum
Leptin Levels and Fat Mass Is Located on Human Chromosome 2
Comuzzie AG; Hixson JE; Almasy L; Mitchell BD; Mahaney MC; Dyer
TD; Stern MP; MacCluer JW; Blangero J
Department of Genetics, Southwest Foundation for Biomedical Research,
San Antonio, Texas 78245-0549, USA. agcom@darwin.sfbr.org
Nature Genetics, 15(3):273-276 (Mar 1997)
Abstract
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.
Variance component linkage analysis