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Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: Association analyses in 9,518 subjects

Lookup NU author(s): Professor Mark Walker

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Abstract

Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial lipodystrophy, a syndrome of monogenic insulin resistance and diabetes. LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components. We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs capturing >90% of common variation) in several large datasets. Analysis of 2,490 U.K. diabetic case and 2,556 control subjects revealed no significant associations at either genotype or haplotype level: the minor allele at rs4641 was no more frequent in case subjects (allelic odds ratio [OR] 1.07 [95% CI 0.98-1.17], P = 0.15). In 390 U.K. trios, family-based association analyses revealed nominally significant overtransmission of the major allele at rs12063564 (P = 0.01), which was not corroborated in other samples. Finally, genotypes for 2,817 additional subjects from the International 1q Consortium revealed no consistent case-control or family-based associations with LMNA variants. Across all our data, the OR for the rs4641 minor allele approached but did not attain significance (1.07 [0.99-1.15], P = 0.08). Our data do not therefore support a major effect of LMNA variation on diabetes risk. However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001). © 2007 by the American Diabetes Association.


Publication metadata

Author(s): Owen KR, Groves CJ, Hanson RL, Knowler WC, Shuldiner AR, Elbein SC, Mitchell BD, Froguel P, Ng MCY, Chan JC, Jia W, Deloukas P, Hitman GA, Walker M, Frayling TM, Hattersley AT, Zeggini E, McCarthy MI

Publication type: Article

Publication status: Published

Journal: Diabetes

Year: 2007

Volume: 56

Issue: 3

Pages: 879-883

ISSN (print): 0012-1797

ISSN (electronic): 1939-327X

Publisher: American Diabetes Association

URL: http://dx.doi.org/10.2337/db06-0930

DOI: 10.2337/db06-0930

PubMed id: 17327460


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Funding

Funder referenceFunder name
Intramural NIH HHS
076113Wellcome Trust
079557Wellcome Trust
G0500070Medical Research Council
K24 DK 2673NIDDK NIH HHS
R01 DK 39311NIDDK NIH HHS
R01 DK054261NIDDK NIH HHS
R01 DK073490NIDDK NIH HHS
R01 DK 073490NIDDK NIH HHS
R01 DK 54261NIDDK NIH HHS
R01 DK039311NIDDK NIH HHS
U01 DK058026NIDDK NIH HHS
T32 AG 00219NIA NIH HHS
T32 AG000219NIA NIH HHS
U01 DK 58026NIDDK NIH HHS

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