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 colla.-en accumulation and elastic loss, risk factors to subsequent aortic enlargement. Therefore, polymorphisins 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), ERalpha PvuII-Xbal (intron 1), ERbeta AluI (exon 8), PR TaqI (intron 7) and TGFbeta1 Bsu361 (-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 ERbeta AtuI restriction site was statistically associated to AAA onset (X-2 = 5.220; OR = 1.82, P < 0.05), ERbeta polymorphism was proposed as genetic determinant in the AAA susceptibility. (C) 2004 Elsevier Ltd. All rights reserved.