Allelic genes involved in artery compliance and susceptibility to sporadic abdominal aortic aneurysm.
Vascular smooth muscle cells (VSMCs) synthesize elastin (ELN), major protein of aortic tunica media which confers strength and elasticity to aortic wall. Protein loss or distortion is typical in aneurysm tunica media. Transforming growth factor beta1 (TGFbeta1) inhibits growth and connective protein expression of abdominal VSMCs cultures. Also, in atherogenic studies, estrogen (but not estrogen plus progestin) treatments inhibit aortic collagen accumulation and elastic loss, risk factors to subsequent aortic enlargement. Therefore, polymorphisms of ELN, estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR) and TGFbeta1 genes and their products may be involved in the abdominal aortic aneurysm (AAA) development. Using PCR-RFLP method, we analyzed ELN RmaI (exon 16), ERalphaPvuII-XbaI (intron 1), ERbetaAluI (exon 8), PR TaqI (intron 7) and TGFbeta1 Bsu36I (-509 bp, promoter) polymorphisms in 324 Caucasian male subjects: 225 healthy controls (mean age 71.20 +/- 6.85 years) and 99 unrelated AAA patients (mean age 69.8 +/- 7.1 years). No difference in ELN, ERalpha, PR and TGFbeta1 allele frequencies was observed in AAA patients versus controls (P > 0.05). However, because possessing at least an ERbetaAluI restriction site was statistically associated to AAA onset (chi(2) = 5.220; OR = 1.82, P < 0.05), ERbeta polymorphism was proposed as genetic determinant in the AAA susceptibility.
Massart
Francesco
F
Pediatric Endocrine Center, Department of Pediatrics, University of Pisa, Via Roma 67, 56125 Pisa, Italy. massart@med.unipo.it
Marini
Francesca
F
Menegato
Alessandra
A
Del Monte
Francesca
F
Nuti
Marco
M
Butitta
Flavio
F
Ferrari
Mauro
M
Balbarini
Alberto
A
Brandi
Maria Luisa
ML
D000368:Aged; D000483:Alleles; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D001158:Arteries / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1