Linkage analysis of candidate obesity genes among the Mexican-American population of Starr County, Texas.
Recent advances in the molecular basis of body fat regulation have identified several genes in which genetic variation may influence obesity and related measures in human populations. Genes that have been shown to have a regulatory function in the control of body fat utilization, eating behavior, and/or metabolic rate in rodent models of obesity include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPY Y1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), and uncoupling protein 1 (UCP1). We have typed microsatellite markers located within or near these seven candidate obesity genes in 302 non-diabetic individuals from 59 Mexican-American families from Starr County, Texas. Sib pair linkage analysis was used to examine linkage between these genes and obesity status (obese siblings only; n = 170 pairs) and several obesity-related quantitative variables (all siblings; n = 545 total sibling pairs). Significant linkage (P = 0.042) was found between obesity and NPY within the obese sibling pairs. No other candidate gene was linked to obesity status in this subsample. Consistent with the obese sib pair linkage results, NPY showed evidence of linkage to body weight (P = 0.020), abdominal circumference (P = 0.031), hip circumference (P = 0.012), diastolic blood pressure (P = 0.005), and a composite measure of body mass and size (P = 0.048) in the entire sibling sample. Other significant linkages observed were between LEP and waist/hip ratio (P = 0.010), total cholesterol (P = 0.030), and HDL cholesterol (P = 0.026) and between LEPR and fasting blood glucose (P = 0.018) and diastolic blood pressure (P = 0.003). These results support further investigation of NPY, LEP, and LEPR to identify genetic variation that may influence obesity status, glucose and lipid metabolism, and blood pressure in Mexican Americans.
Bray
M S
MS
Human Genetics Center, University of Texas-Houston Health Science Center, Graduate School of Biomedical Sciences 77225, USA.
Boerwinkle
E
E
Hanis
C L
CL
D000328:Adult; D000886:Anthropometry; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005934:Glucagon / Q000235:genetics; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007473:Ion Channels; D020738:Leptin; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D017058:Mexican Americans / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y / Q000235:genetics; D009765:Obesity / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010446:Peptide Fragments / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon / Q000235:genetics; D054411:Receptors, Leptin; D017476:Receptors, Neuropeptide Y / Q000235:genetics; D013781:Texas; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D054411:Receptors, Leptin; D017476:Receptors, Neuropeptide Y; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D052216:Glucagon-Like Peptide 1; D005934:Glucagon