Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids.
OBJECTIVE
In the present study, we sought to examine the evidence that LMNA variants are associated with type 2 diabetes and quantitative metabolic traits in French Europid individuals.


METHODS
We genotyped 24 single nucleotide polymorphisms (SNPs) spanning the LMNA gene in 3,093 case-control participants. The association between LMNA SNPs and quantitative metabolic traits was also examined in the 1,674 normoglycaemic adults who made up the control cohort.


RESULTS
SNP rs505058, a synonymous SNP (D446D) in exon 7, showed nominal evidence of association with type 2 diabetes [p = 0.003, odds ratio (OR) 1.30 (95% CI 1.09-1.56)] in French Europids. A meta-analysis of available rs505058 genotype data from 7,819 participants provided support for a modest association of rs505058 with type 2 diabetes [p = 0.003, OR 1.19 (95% CI 1.06-1.35)]. We found no evidence (p = 0.91) that the tag SNP rs4641 is associated with type 2 diabetes. However, a meta-analysis of all available rs4641 genotype data in a total of 15,591 participants produced borderline evidence of association [p = 0.054, OR 1.05 (95% CI 1.00-1.11)]. SNP rs6669212, in the 3' untranslated region of LMNA, exhibited suggestive associations with WHR (p = 0.013), fasting serum levels of total cholesterol (p = 0.023) and triacylglycerol (p = 0.015). We emphasise that these quantitative trait associations are not corrected for multiple testing.


CONCLUSIONS
The available data do not support a major effect of common LMNA variation on type 2 diabetes susceptibility in northern Europeans. Further large-scale studies are required to conclusively establish the extent to which LMNA variants have an impact on quantitative metabolic traits.
Duesing
K
K
Genomic Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Charpentier
G
G
Marre
M
M
Tichet
J
J
Hercberg
S
S
Froguel
P
P
Gibson
F
F
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005602:France; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008660:Metabolism / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
C494847:LMNA protein, human; D034904:Lamin Type A; D014280:Triglycerides; D002784:Cholesterol