Lamin A/C Polymorphisms, Type 2 Diabetes, and the Metabolic Syndrome
Case-Control and Quantitative Trait Studies
- José L. Mesa1,
- Ruth J.F. Loos1,
- Paul W. Franks12,
- Ken K. Ong1,
- Jian’an Luan1,
- Stephen O’Rahilly3,
- Nicholas J. Wareham1 and
- Inês Barroso4
- 1Medical Research Center Epidemiology Unit, Cambridge, U.K
- 2Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden
- 3University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Cambridge, U.K
- 4Metabolic Disease Group, The Wellcome Trust Sanger Institute, Hinxton, U.K
- Address correspondence and reprint requests to Inês Barroso, PhD, The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, U.K. E-mail: ib1{at}sanger.ac.uk
Abstract
Mutations in the LMNA gene, encoding the nuclear envelope protein lamin A/C, are responsible for a number of distinct disease entities including Dunnigan-type familial partial lipodystrophy. Dunningan-type lipodystrophy is characterized by loss of subcutaneous adipose tissue, insulin resistance, dyslipidemia, and type 2 diabetes and shares many of the features of the metabolic syndrome. Furthermore, several genome-wide linkage scans for type 2 diabetes have found evidence of linkage at chromosome 1q21.2, the region that harbors the LMNA gene. Therefore, LMNA is a biological and positional candidate for type 2 diabetes susceptibility. Previous studies have reported association between a common LMNA variant (1908C>T; rs4641) and adverse metabolic traits in ethnically diverse populations from Asia and North America. In the present study, we characterized the common variation across the LMNA gene (including rs4641) and tested for association with type 2 diabetes in two large case-control studies (n = 2,052) and with features of the metabolic syndrome in a separate cohort study (n = 1,572). Despite our study being sufficiently powered to detect effects similar and even smaller in magnitude than those previously reported, none of the LMNA single nucleotide polymorphisms were statistically significantly associated with type 2 diabetes or the metabolic syndrome. Thus, it appears unlikely that variation at LMNA substantially increases the risk of type 2 diabetes or related traits in U.K. Europids.
- CCC, Cambridgeshire Case-Control
- EPIC, European Prospective Investigation into Cancer
- FPLD, familial partial lipodystrophy
- LD, linkage disequilibrium
- MAF, minor allele frequency
- MRC, Medical Research Council
- SNP, single nucleotide polymorphism
Footnotes
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Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1055.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted December 12, 2006.
- Received July 28, 2006.
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