Journal of Molecular Medicine

, Volume 88, Issue 2, pp 193–201 | Cite as

Polymorphisms of the lamina maturation pathway and their association with the metabolic syndrome: the DESIR prospective study

  • Benedicte Fontaine-Bisson
  • Marie-Christine Alessi
  • Noemie Saut
  • Frederic Fumeron
  • Michel Marre
  • Anne Dutour
  • Catherine Badens
  • Nicolas Levy
  • Jean Tichet
  • Irene Juhan-Vague
  • David-Alexandre Trégouët
  • Beverly Balkau
  • Pierre-Emmanuel MorangeEmail author
Original Article


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.


Metabolic 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

Supplementary material

109_2009_548_MOESM1_ESM.pdf (87 kb)
Supplementary Table Supplementary Table 1: haplotype frequencies according to case–control status in the DESIR cohort for the five genes in the lamina maturation pathway. Supplementary Table 2: linkage disequilibrium (D′) matrix for the five genes of the lamina maturation pathway estimated in controls. Supplementary Table 3: allele frequency and genotype distribution of the 23 polymorphisms in the lamina maturation pathway according to the case–control (n = 509/2,878) status in the DESIR cohort—incidence analysis. Supplementary Table 4: combined effect of polymorphisms in the lamina maturation pathway on MS risk—incidence analysis. Supplementary Table 5A: association between LMNA haplotypes and each component of the metabolic syndrome in the DESIR cohort (baseline data). Supplementary Table 5B: association between FNTA haplotypes and each component of the metabolic syndrome in the DESIR cohort (baseline data). Supplementary Table 5C: association between FNTB haplotypes and each component of the metabolic syndrome in the DESIR cohort (baseline data). Supplementary Table 5D: association between ZEMPSTE24 haplotypes and each component of the metabolic syndrome in the DESIR cohort (baseline data). Supplementary Table 5E: association between ICMT haplotypes and each component of the metabolic syndrome in the DESIR cohort (baseline data). Supplementary Table 6: Allele frequency and genotype distribution of the 23 polymorphisms in the lamina maturation pathway according to the type II diabetes case–control (n = 251/3,665) status+ in the DESIR cohort. Supplementary Table 7: power to detect the observed associations at the studied SNPs for a significance level of 0.05. (PDF 86 kb)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Benedicte Fontaine-Bisson
    • 1
    • 2
  • Marie-Christine Alessi
    • 3
    • 4
  • Noemie Saut
    • 3
    • 4
  • Frederic Fumeron
    • 5
    • 6
  • Michel Marre
    • 5
    • 6
  • Anne Dutour
    • 3
    • 4
  • Catherine Badens
    • 7
  • Nicolas Levy
    • 7
  • Jean Tichet
    • 8
  • Irene Juhan-Vague
    • 3
    • 4
  • David-Alexandre Trégouët
    • 1
    • 2
  • Beverly Balkau
    • 9
    • 10
  • Pierre-Emmanuel Morange
    • 3
    • 4
    • 11
    Email author
  1. 1.INSERM, UMR_S 937ParisFrance
  2. 2.UPMC Univ Paris 06, UMR_S 937ParisFrance
  3. 3.INSERM, UMR_S 626MarseilleFrance
  4. 4.Université de la MéditerranéeMarseilleFrance
  5. 5.INSERM U695, Xavier Bichat Medical SchoolParisFrance
  6. 6.University Paris Diderot—Paris 7ParisFrance
  7. 7.INSERM U910MarseilleFrance
  8. 8.Regional Institute for HealthToursFrance
  9. 9.INSERM U780-IFR69ParisFrance
  10. 10.University of Paris-SudParisFrance
  11. 11.Laboratory of HaematologyCHU TimoneMarseille cedex 05France

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