Low transcriptional activity haplotype of matrix metalloproteinase 1 is less frequent in bicuspid aortic valve patients

• We proposed an association between MMP1 polymorphisms and aortic valve pathology.
• Lower transcriptional activity MMP1 haplotypes are less frequent in BAV patients.
• More active MMP1 allele and genotype are more frequent in male TAA patients.
• Functional MMP1 genetic variants correlate with aortic valve pathology.

PurposeBicuspid aortic valve (BAV) is the most common congenital cardiac anomaly which affects 0.5–2% of the population. It can be associated with other cardiac congenital lesions such as aortic aneurysms or aortic coarctation. Some genetic abnormalities have been suggested as the underlying cause of BAV and aortic root dilatation, but no clear genetic substrate and no specific pathogenic gene variant have already been identified. Increased matrix metalloproteinase activity has been described in the aortic wall of thoracic aortic aneurysms (TAA).Methods87 patients with BAV and 77 controls with normal tricuspid aortic valve were prospectively assessed. We analysed three functional polymorphisms (− 1607 1G/2G, − 519 A/G, and − 340 T/C) in the matrix metalloproteinase (MMP)-1 gene using polymerase chain reaction and restriction fragment length analysis.ResultsWe found a haplotype composed of the lower activity allele from each polymorphism (− 1607 1G/− 519 A/− 340 C) significantly less frequent in BAV group (p = 0.016; OR [95% CI] = 0.37 [0.16–0.85]), association even more clear when we consider only men (p = 0.0005, OR [95% CI] = 0.24 [0.10–0.56]).We also found a borderline statistical significance in the distribution of the − 1607 alleles, being 2G allele more frequent in patients with TAA (p = 0.053). This association was stronger and statistically significant when we consider only men (p = 0.013; OR [95% CI] = 2.0 [1.16–3.50]). In addition, genotype − 1607 2G2G, theoretically the more active transcriptionally, was also significantly more frequent in TAA group, independently of aortic valve morphology.ConclusionsOur study suggests that specific genotypes of MMP1 gene could be in part responsible of the complications of BAV pathology, like TAA.