Matrix metalloproteainase-3 polymorphism association with hypertrophic cardiomyopathy

Background Matrix metalloproteinase-3 (MMP-3) level disequilibrium in hypertrophic cardiomyopathy (HCM) may be due to a specific genetic variation. The MMP-3 gene promoter contains an insertion/deletion polymorphism characterized by an array of 5 or 6 adenosine residues (5A/6A) at –1612 positions. Purpose The aim was to analyze whether the MMP-3 5A/6A gene promoter polymorphism is related to its level in HCM patients. Methods/Results In this study, we recruited 33 HCM patients and 35 non-HCM. The ELISA sandwich assay measured MMP-3 plasmatic level. The MMP-3 –1612 5A/6A polymorphism was genotyped by RFLP-PCR. The studied population was consistentin Hardy-Weinberg equilibrium. There were 17% 5A/5A homozygotes, 65% 6A/6A homozygotes, and 17% 5A/6A heterozygotes. The HCM was related to the existence of the –1612 5A/6A polymorphism (p<0.05). Patients carrying the 5A allele had a higher MMP-3 level than those with the 6A allele (16.03±9.43 vs 8.68±5.89 ng/ml, respectively; p=0.01). Conclusion Our data shows that the –1612 5A/6A MMP-3 gene polymorphism is associated to the hypertrophic cardiomyopathy and do influence the MMP-3 plasmatic circulating level. Funding Acknowledgement Type of funding source: None

The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

Liver X receptors (LXRs) have emerged as important regulators of inflammatory gene expression. Previously, we had reported that an LXRα gene promoter polymorphism (-1830 T > C) is associated with systemic lupus erythematosus (SLE). Therefore, we assessed cytokine expression in relation to LXRα polymorphism in monocyte-derived macrophages from patients with SLE. Macrophages were obtained after 72 hours of culture of human monocytes supplemented with phorbol 12-myristate 13-acetate. Cells were transfected with LXRα promoter constructs. Additionally, peripheral blood mononuclear cell- (PBMC-) derived macrophages from the patients were evaluated for proinflammatory cytokines in relation to the genotypes of LXRα -1830 T > C. The expression of LXRα was increased in macrophages; levels of proinflammatory cytokines were decreased with LXRα expression. Production of proinflammatory cytokines varied depending on LXRα -1830 T > C genotype. In particular, expression of LXRα was decreased and that of proinflammatory cytokines was increased for LXRα -1830 TC genotype compared to that for TT genotype. The data were consistent in PBMC-derived macrophages from patients with SLE. Increased proinflammatory cytokines is related to TLR7 and TLR9 expression. These data suggest that the expression levels of LXRα, according to LXRα -1830 T > C genotype, may contribute to the inflammatory response by induction of inflammatory cytokines in SLE.