Details

Autor(en) / Beteiligte

• OWEN, Katharine R
• GROVES, Christopher J
• WEIPING JIA
• DELOUKAS, Panos
• HITMAN, Graham A
• WALKER, Mark
• FRAYLING, Timothy M
• HATTERSLEY, Andrew T
• ZEGGINI, Eleftheria
• MCCARTHY, Mark I
• HANSON, Robert L
• KNOWLER, William C
• SHULDINER, Alan R
• ELBEIN, Steven C
• MITCHELL, Braxton D
• FROGUEL, Philippe
• NG, Maggie C. Y
• CHAN, Juliana C

Titel

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

Ist Teil von

• Diabetes (New York, N.Y.), 2007-03, Vol.56 (3), p.879-883

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2007

Link zum Volltext

Quelle

Open access e-journals list

Beschreibungen/Notizen

• 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).