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).
journal_name
Diabetesjournal_title
Diabetesauthors
Owen KR,Groves CJ,Hanson RL,Knowler WC,Shuldiner AR,Elbein SC,Mitchell BD,Froguel P,Ng MC,Chan JC,Jia W,Deloukas P,Hitman GA,Walker M,Frayling TM,Hattersley AT,Zeggini E,McCarthy MIdoi
10.2337/db06-0930subject
Has Abstractpub_date
2007-03-01 00:00:00pages
879-83issue
3eissn
0012-1797issn
1939-327Xpii
56/3/879journal_volume
56pub_type
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