Polymorphisms of the lamina maturation pathway and their association with the metabolic syndrome: the DESIR prospective study.
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.
INSERM, UMR_S 937, 75013, Paris, France.
Benedicte
B
Fontaine-Bisson
Marie-Christine
MC
Alessi
Noemie
N
Saut
Frederic
F
Fumeron
Michel
M
Marre
Anne
A
Dutour
Catherine
C
Badens
Nicolas
N
Levy
Jean
J
Tichet
Irene
I
Juhan-Vague
David-Alexandre
DA
Trégouët
Beverly
B
Balkau
Pierre-Emmanuel
PE
Morange
D000328:Adult; D000368:Aged; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D034882:Lamins / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins; D011506:Proteins