Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians

We previously showed that a rare mutation in LMNA, which encodes lamins A a nd C, underlies autosomal dominant Dunnigan-type familial partial lipodystr ophy (FPLD). Because FPLD is an extreme example of genetically disturbed ad ipocyte differentiation, it is possible that common variation in LMNA is as sociated with obesity-related phenotypes. We therefore analyzed the relatio nships between the common LMNA 1908T/C single nucleotide polymorphism (SNP) and plasma leptin and anthropometric indices in 306 nondiabetic Canadian O ji-Cree. We found that subjects with the LMNA 1908T/1908T genotype had sign ificantly higher plasma leptin than the subjects with either the 1908C/1908 T or 1908C/1908C genotypes, after adjustment for age and sex. Physical indi ces of obesity, such as body mass index, percent body fat, and ratio of wai st-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.