Quantitative Trait Loci on Chromosomes 3 and 17 Influence Phenotypes of the Metabolic Syndrome

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 26; pp. 14478 - 14483
• Main Authors: Kissebah, A H, Sonnenberg, G E, Myklebust, J, Goldstein, M, Broman, K, James, R G, Marks, J A, Krakower, G R, Jacob, H J, Weber, J, Martin, L, Blangero, J, Comuzzie, A G
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 19.12.2000; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Biological Sciences; Blood Glucose - analysis; Body mass index; chromosome 3; chromosome 7; Chromosomes; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 3; Circumferences; dyslipidemia; European Continental Ancestry Group; Genes; Genetic Linkage; Genetics; glucose intolerance; high blood pressure; Humans; Insulin; Insulin - blood; leptin; Leptin - blood; Lipid metabolism; Lod score; metabolic syndrome; Metabolism; Obesity; Obesity - blood; Obesity - genetics; Phenotype; Phenotypes; Quantitative trait loci; Quantitative Trait, Heritable
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.97.26.14478

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.