title: Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians.
abstract: We previously showed that a rare mutation in LMNA, which encodes lamins A and C, underlies autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD). Because FPLD is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We therefore analyzed the relationships between the common LMNA 1908T/C single nucleotide polymorphism (SNP) and plasma leptin and anthropometric indices in 306 nondiabetic Canadian Oji-Cree. We found that subjects with the LMNA 1908T/1908T genotype had significantly higher plasma leptin than the subjects with either the 1908C/1908T or 1908C/1908C genotypes, after adjustment for age and sex. Physical indices of obesity, such as body mass index, percent body fat, and ratio of waist-to-hip circumference, were also higher among Oji-Cree subjects with the LMNA 1908T/1908T genotype than the subjects with either the 1908C/1908T or 1908C/1908C genotypes. The results suggest that common genetic variation in LMNA may be an important determinant of plasma leptin and obesity-related quantitative traits.
authors.affiliation: John P. Robarts Research Institute, Centre for Studies in Family Medicine, University of Western Ontario, London, Ontario N6A 5K8, Canada. robert.hegele@rri.on.ca
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.forename: S B
authors.initials: SB
authors.lastname: Harris
authors.forename: B
authors.initials: B
authors.lastname: Zinman
authors.forename: A J
authors.initials: AJ
authors.lastname: Hanley
authors.forename: C M
authors.initials: CM
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001823:Body Composition / Q000235:genetics; D001824:Body Constitution / Q000235:genetics; D015992:Body Mass Index; D002170:Canada / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D034882:Lamins; D020738:Leptin / Q000097:blood* / Q000235:genetics; D008297:Male; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable
chemical_list: D034882:Lamins; D020738:Leptin; D009687:Nuclear Proteins