Polymorphisms of the lamina maturation pathway and their association with the metabolic syndrome: the DESIR prospective study
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Laminopathies are rare monogenic diseases, some of them exhibiting features of the metabolic syndrome. These diseases are mainly due to mutations in LMNA, encoding A-type lamins. One LMNA polymorphism, rs4641, has been associated with the metabolic syndrome, but results have been controversial. We therefore investigated the effect of single nucleotide polymorphisms (SNPs) in the LMNA gene in combination with four other genes encoding enzymes influencing lamin post-translational maturation on risk of metabolic syndrome (MS). Twenty-three tagging SNPs characterising the haplotypic variability of five genes (LMNA, ICMT, ZMPSTE24, FNTA and FNTB) were genotyped in 3,916 French men and women who took part in the prospective DESIR study. Single locus and haplotype analyses were performed but did not detect any significant association with the risk of MS. No robust interaction between SNPs located in different genes on the risk of MS was identified. In conclusion, we did not observe any convincing evidence that common polymorphisms of the lamina pathway could modulate the risk of MS.
KeywordsMetabolic syndrome Diabetes Lamin A Polymorphisms Association studies
The DESIR study was supported by the Programme Hospitalier de Recherche Clinique (PHRC), INSERM-CNAMTS (Caisse Nationale de l’Assurance Maladie des Travailleurs Salariés), Lilly, Novartis Pharma, Sanofi-Aventis, INSERM (Réseaux en Santé Publique, Interactions entre les determinants de la santé), the Association Diabète Risque Vasculaire, the Fédération Française de Cardiologie, La Fondation de France, ALFEDIAM, Onivins, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche and Topcon. Bénédicte Fontaine-Bisson was a recipient of a post-doctoral fellowship from the Ile-de-France region.
Members of the DESIR Study Group
INSERM U780: B. Balkau, P. Ducimetière, E. Eschwège; INSERM U367: F. Alhenc-Gelas; CHU D’Angers: Y. Gallois, A. Girault; Bichat Hospital: F. Fumeron, M. Marre; CNRS UMR8090, LILLE: P. Froguel; Centres d'Examens de Santé: Alençon, Angers, Caen, Chateauroux, Cholet, Le Mans, Tours; Institute de Recherche Médecine Générale: J. Cogneau; General practitioners of the region; Institut Inter-régional pour la Santé: C. Born, E. Caces, M. Cailleau, J.G. Moreau, F. Rakotozafy, J. Tichet, S. Vol.
We have no conflict of interest to declare
- 1.Vantyghem MC, Pigny P, Maurage CA, Rouaix-Emery N, Stojkovic T, Cuisset JM, Millaire A, Lascols O, Vermersch P, Wemeau JL et al (2004) Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J Clin Endocrinol Metab 89:5337–5346CrossRefPubMedGoogle Scholar
- 7.Wegner L, Andersen G, Sparso T, Grarup N, Glümer C, Borch-Johnsen K, Jørgensen T, Hansen T, Pedersen O (2007) Common variation in LMNA increases susceptibility to type 2 diabetes and associates with elevated fasting glycemia and estimates of body fat and height in the general population: studies of 7,495 Danish whites. Diabetes 56:694–698CrossRefPubMedGoogle Scholar
- 13.Weyer C, Wolford JK, Hanson RL, Foley JE, Tataranni PA, Bogardus C, Pratley RE (2001) Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked to chromosome 1q21–q23 and is associated with a common polymorphism in LMNA in Pima Indians. Mol Genet Metab 72:231–238CrossRefPubMedGoogle Scholar
- 25.Vari IS, Balkau B, Kettaneh A, Andre P, Tichet J, Fumeron F, Caces E, Marre M, Grandchamp B, Ducimetiere P (2007) Ferritin and transferrin are associated with metabolic syndrome abnormalities and their change over time in a general population: Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 30:1795–1801CrossRefPubMedGoogle Scholar