title: Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome.
abstract: Recent research has emphasized the importance of the metabolic cluster, which includes glucose intolerance, dyslipidemia, and high blood pressure, as a strong predictor of the obesity-related morbidities and premature mortality. Fundamental to this association, commonly referred to as the metabolic syndrome, is the close interaction between abdominal fat patterning, total body adiposity, and insulin resistance. As the initial step in identifying major genetic loci influencing these phenotypes, we performed a genomewide scan by using a 10-centiMorgan map in 2,209 individuals distributed over 507 nuclear Caucasian families. Pedigree-based analysis using a variance components linkage model demonstrated a quantitative trait locus (QTL) on chromosome 3 (3q27) strongly linked to six traits representing these fundamental phenotypes [logarithm of odds (lod) scores ranged from 2.4 to 3.5]. This QTL exhibited possible epistatic interaction with a second QTL on chromosome 17 (17p12) strongly linked to plasma leptin levels (lod = 5.0). Situated at these epistatic QTLs are candidate genes likely to influence two biologic precursor pathways of the metabolic syndrome.
authors: Take Off Pounds Sensibly (TOPS) Center for Obesity and Metabolic Research, and the Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. vdodge@mcw.edu
authors: A H
authors: AH
authors: Kissebah
authors: G E
authors: GE
authors: Sonnenberg
authors: J
authors: J
authors: Myklebust
authors: M
authors: M
authors: Goldstein
authors: K
authors: K
authors: Broman
authors: R G
authors: RG
authors: James
authors: J A
authors: JA
authors: Marks
authors: G R
authors: GR
authors: Krakower
authors: H J
authors: HJ
authors: Jacob
authors: J
authors: J
authors: Weber
authors: L
authors: L
authors: Martin
authors: J
authors: J
authors: Blangero
authors: A G
authors: AG
authors: Comuzzie
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D008040:Genetic Linkage; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin