Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids

Aims/hypothesis 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/interpretation 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.