PP.23.11] MATRIX METALLOPROTEINASE 2 GENE POLYMORPHISM ASSOCIATES WITH RESISTANT HYPERTENSION

Abstract

Objective: The lack of blood pressure (BP) control (>140/90 mmHg) – even in the presence of three or more antihypertensive drugs of different classes - define the hypertensive patients at high cardiovascular (CV) risk and high incidence of target organ damage (TOD) as resistant hypertensives (RH). Studies suggest the involvement of metalloproteinase 2 (MMP-2) in hypertension and in CV remodeling associated with TOD. Hypertension is a multifactorial condition in which BP heritability and genetic factors may have a large contribution in the development of the disease. MMP-2 single nucleotide polymorphisms (SNPs) have been associated with the predisposition of CV alterations. Few studies have evaluated the impact of MMP-2 polymorphisms on clinical conditions and their influence in RH is unknown. The aim of this study is to analyze the influence of MMP-2 SNPs in RH, as well as their association with TOD in this high CV risk group. Design and method: 119 RH patients and 136 mild to moderate hypertensives (HT) were included and submitted to clinical and laboratorial evaluations. We assessed genotypes by allelic discrimination assay using real time polymerase chain reaction. We compare clinical and laboratorial characteristics according to SNPs genotypes/haplotypes (rs243865, rs243866 and rs2285053). TOD were categorized by left ventricular mass index (women >95 g/m2 and men >115 g/m2) and arterial stiffness (PWV>10m/s). Results: We did not find association of studied SNPs with TOD and clinical features. However, the allelic and genotype frequencies of rs2285053 showed to be different between RH and HT subjects (C vs T, p = 0.02; CC vs CT vs TT, p = 0.04, respectively), with high prevalence of C allele in the RH group. Moreover, haplotype frequencies were also different (GCC vs GCT vs ATC, p = 0.03) between groups. Finally, regression analysis demonstrated that haplotype was associated with resistance to treatment, as well as age, gender, race, BMI, LVH and aldosterone levels. Conclusions: We conclude that only the SNP rs2285053 may be associated with RH when compared to controlled counterparts. Our finding suggests that the presence of C allele may have some bearing in the resistance to antihypertensive process.