A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2.
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.
Comuzzie
A G
AG
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245-0549, USA. agcom@darwin.sfbr.org
Hixson
J E
JE
Almasy
L
L
Mitchell
B D
BD
Mahaney
M C
MC
Dyer
T D
TD
Stern
M P
MP
MacCluer
J W
JW
Blangero
J
J
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000704:Analysis of Variance; D001161:Arteriosclerosis / Q000235:genetics; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D020738:Leptin; D008126:Lod Score; D008297:Male; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000378:metabolism*; D012307:Risk Factors
D005819:Genetic Markers; D020738:Leptin; D011506:Proteins