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Common Variation in the LMNA Gene (Encoding Lamin A/C) and Type 2 Diabetes.
- Source :
- Diabetes; Mar2007, Vol. 56 Issue 3, p879-883, 5p, 3 Charts
- Publication Year :
- 2007
-
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). Diabetes 56:879-883, 2007 [ABSTRACT FROM AUTHOR]
- Subjects :
- DIABETES
TYPE 2 diabetes
HYPOGLYCEMIC agents
INSULIN resistance
GENETIC research
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 56
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 24497703
- Full Text :
- https://doi.org/10.2337/db06-0930