Sex-specific effect of matrix Metalloproteinase-9 functional promoter polymorphism on carotid artery stiffness

Background and PurposeLarge artery stiffness is considered to be a marker for cardiovascular disease. Serum matrix metalloproteinase-9 (MMP-9) level has been found to correlate with arterial stiffness and predict cardiovascular risk. This study was aimed to investigate the relationship between the MMP-9 genotypes and artery stiffness, and to examine whether the genetic effect is sex specific.MethodsThree carotid stiffness modalities were assessed in 1218 (704 females) stroke- and myocardial infarction-free volunteers aged 21-86 years old. The genotypes of MMP-9 promoter polymorphism (-1562C/T) were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Analysis was conducted to test for the overall and sex specific effect using multivariate regression model.ResultsT allele carriers (CT and TT) had stiffer arteries than CC homozygotes after adjusting for age and sex (p = 0.013, 0.028, and 0.017 for Ep, β, and PWV, respectively). Further sex-stratified analysis showed that the significant association only existed in women. Women with the T allele had significantly stiffer arteries than CC homozygotes after adjusting for age (p = 0.003, 0.018, and 0.006 for Ep, β, and PWV, respectively), and this association remained significant after adjusting for known covariates. When menopausal status was further considered, all three carotid stiffness modalities were significantly different between T allele carriers and CC homozygotes in menopausal but not in pre-menopausal women.ConclusionsThis study indicates that individuals carrying the -1562T allele are predisposed to stiffer arteries, especially among menopausal women. Women with the T allele should be considered at high risk for cardiovascular disease.

► We study the relationship of MMP-9 on carotid stiffness in 1218 healthy subjects. ► The T allele of MMP-9 -1562C/T is associated with stiffer arteries. ► The significant association only in women, not in men. ► Comparing by menopausal status, the association was only in menopausal women.