• Stern, Rf
• Lewis, Cathryn
• Solomon, E.
• Deguara, J.
• Taylor, P.
• Berg, J.
• Burnand, Kg
• Green, P.
• Smith, Alberto
• Waltham, M.
• Chinien, G.

Abstract

Matrix metalloproteinase 3 (MMP3), is over expressed in the wall of abdominal aortic aneurysms (AAA), while inactivation of the gene expressing this enzyme is associated with reduced aneurysm formation in an experimental model. The 5A allele of the 5A/6A polymorphism in the promoter region of the MMP3 gene is associated with enhanced MMP3 expression. This study aimed to determine whether the presence of the 5A allele in the MMP3 promoter is a risk factor for AAA, and if this allele is associated with an increased expression of MMP3 in the aneurysm wall. We compared the frequencies of the 5A and 6A alleles in AAA (n=405), aortic occlusive disease (AOD) (n=123) and controls (n=405). The 5A allele frequency was higher in AAA compared with controls (odds ratio - OR 1.32, P=0.005) and AOD (OR 1.684, P=0.0004), but was similar in AOD compared to controls (OR 0.78, P=0.1). The ORs of the 5A/6A and the 5A/5A genotypes were 1.35 and 1.79, compared with 6A homozygotes. Although wall from 5A homozygotes contained 17% more MMP3 mRNA than homozygotes (P=0.049) the significance of this was lost when adjusted for age and sex (P=0.069), and size (P=0.30). Wall from 5A homozygotes did however contain over 45% more MMP3 protein than heterozygotes (P=0.009 when corrected for age and sex and P=0.043 when corrected for aneurysm size). It appears that an abnormality in the MMP3 gene is part of the genetic profile that predisposes to aneurysmal disease

Topics

• impedance spectroscopy