Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study
| Autor: | Chagnon, Y. C., Chen, W. J., Louis Perusse, Chagnon, M., Nadeau, A., Wilkison, W. O., Bouchard, C. |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Analysis of Variance Adolescent Receptors Peptide Genetic Linkage Receptors Melanocortin Quebec Middle Aged Glucose Receptors Corticotropin Homeostasis Humans Insulin Receptor Melanocortin Type 4 Female Tissue Distribution Obesity Energy Metabolism Polymorphism Restriction Fragment Length Research Article Aged |
| Zdroj: | ResearcherID |
| Popis: | BACKGROUND: The agouti yellow mouse shows adult onset of moderate obesity and diabetes. A depressed basal lipolytic rate in adipocytes or a decreased adrenergic tone arising from antagonizing alpha-melanocyte-stimulating hormone (MSH) activation of melanocortin receptors (MCR) could be at the origin of the obesity phenotype. MATERIAL AND METHODS: MCR 4 and 5 (MC4R, MC5R) genes were studied in the Québec Family Study. Sequence variations were detected by Southern blot probing of restricted genomic DNA, and mRNA tissue expression was detected by RT-PCR. Subjects with a wide range of weight were used for single-point sib-pair linkage studies (maximum of 289 sibships from 124 nuclear families). Analysis of variance across genotypes in unrelated males (n = 143) and females (n = 156) was also undertaken. Body mass index (BMI), sum of six skin-folds (SF6), fat mass (FM), percent body fat (%FAT), respiratory quotient (RQ), resting metabolic rate (RMR), fasting glucose and insulin, and glucose and insulin area during an oral glucose tolerance test were analyzed. RESULTS: MC4R showed polymorphism with NcoI, and MC5R, with PstI and PvuII, with a heterozygosity of 0.38, 0.10, and 0.20, respectively. Linkages were observed between MC5R and BMI (p = 0.001), SF6 (p = 0.005), FM (p = 0.001), and RMR (p = 0.002), whereas associations were observed in females between MC5R and BMI (p = 0.003), and between MC4R and FM (p = 0.002) and %FAT (p = 0.004). After correction for multiple tests, these p values are lowered by one tenth. MC4R and MC5R mRNAs have been detected in brain, adipose tissue, and skeletal muscle. CONCLUSIONS: MC4R and MC5R exhibit evidence of linkage or association with obesity phenotypes, but this evidence is strongest for MC5R. |
| Databáze: | OpenAIRE |
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