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Common Genomic Variation in LMNA Modulates Indexes of Obesity in Inuit¹

John P. Robarts Research Institute (R.A.H., M.W.H.), London, Ontario, Canada N6A 5K8; and Department of Community Health Sciences, University of Manitoba (T.K.Y.), Winnipeg, Manitoba, Canada R3E 0W3

Address all correspondence and requests for reprints to: Robert A. Hegele, M.D., Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406–100 Perth Drive, London, Ontario, Canada N6A 5K8. E-mail: robert.hegele{at}rri.on.ca

Abstract

We discovered that rare mutations in LMNA, which encodes lamins A and C, underlie autosomal dominant Dunnigan-type familial partial lipodystrophy. Because familial partial lipodystrophy is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We subsequently discovered a common single nucleotide polymorphism (SNP) in LMNA, namely 1908C/T, which was associated with obesity-related traits in Canadian Oji-Cree. We now report association of this LMNA SNP with anthropometric indexes in 186 nondiabetic Canadian Inuit. We found that physical indexes of obesity, such as body mass index, waist circumference, waist to hip circumference ratio, subscapular skinfold thickness, and subscapular to triceps skinfold thickness ratio were each significantly higher among Inuit subjects with the LMNA 1908T allele than in subjects with the 1908C/1908C genotype. For each significantly associated obesity-related trait, the LMNA 1908C/T SNP genotype accounted for between approximately 10–100% of the attributable variation. The results indicate that common genetic variation in LMNA is an important determinant of obesity-related quantitative traits.

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