Ritter Alessandra M V, de Faria Ana Paula, Barbaro Natália R, Sabbatini Andréa R, Corrêa Nathália Batista, Brunelli Veridiana, Fattori Andre, Amorim Rivadavio, Modolo Rodrigo, Moreno Heitor
Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
Gene. 2018 Mar 10;646:129-135. doi: 10.1016/j.gene.2017.12.023. Epub 2017 Dec 27.
We sought to investigate whether the polymorphisms rs243865 (-1306C>T); rs243866 (-1575G>A) and rs2285053 (-735C>T) in metalloproteinases 2 - MMP-2 gene and rs17576 (Q279R), rs17577 (Q668R) and rs3918242 (-1562C>T) in MMP-9 gene are associated with clinical outcomes in obese resistant hypertensive (RH) subjects. One hundred and twenty RH were enrolled in this cross-sectional study and divided into obese (n=63) and non-obese (n=57) according to body mass index. Genotypes were determined by real-time PCR using TaqMan probes. We determined pulse wave velocity (PWV), microalbuminuria and left ventricular mass index (LVMI) to assess TODs. Obese and non-obese RH had similar allele, genotype and haplotype distributions for all polymorphisms assessed but obese RH subjects carrying the low frequency allele for SNPs in MMP-2 gene had higher ambulatory diastolic blood pressure. Also, PWV and LVMI were higher in subjects carrying the low frequency allele for SNPs in MMP-2 gene. Regarding MMP-9 gene, office diastolic BP levels were higher in the AA genotype individuals compared to the G allele group for rs17576 polymorphism, while the opposite was found regarding the microalbuminuria level. Independent multiple linear regression analyses revealed that both A allele for rs243865 and T allele for rs243866 in MMP-2 gene were associated with ambulatory diastolic levels in obese RH subjects, apart from potential confounders. Our study suggests that rs243866/rs243865 in the MMP-2 gene are related to BP levels in obese RH subjects, although TODs present in this population seem to be dependent of a combination of other factors besides the genetic polymorphisms.
我们试图研究金属蛋白酶2（MMP - 2）基因中的多态性rs243865（-1306C>T）、rs243866（-1575G>A）和rs2285053（-735C>T）以及MMP - 9基因中的多态性rs17576（Q279R）、rs17577（Q668R）和rs3918242（-1562C>T）是否与肥胖抵抗性高血压（RH）患者的临床结局相关。120例RH患者参与了这项横断面研究，并根据体重指数分为肥胖组（n = 63）和非肥胖组（n = 57）。使用TaqMan探针通过实时PCR确定基因型。我们测定了脉搏波速度（PWV）、微量白蛋白尿和左心室质量指数（LVMI）以评估靶器官损害（TODs）。肥胖和非肥胖的RH患者在所有评估的多态性中具有相似的等位基因、基因型和单倍型分布，但携带MMP - 2基因SNP低频等位基因的肥胖RH患者动态舒张压较高。此外，携带MMP - 2基因SNP低频等位基因的患者PWV和LVMI较高。关于MMP - 9基因，对于rs17576多态性，AA基因型个体的诊室舒张压水平高于G等位基因组，而在微量白蛋白尿水平方面则相反。独立多元线性回归分析显示，除了潜在的混杂因素外，MMP - 2基因中rs243865的A等位基因和rs243866的T等位基因均与肥胖RH患者的动态舒张压水平相关。我们的研究表明，MMP - 2基因中的rs243866/rs243865与肥胖RH患者的血压水平相关，尽管该人群中存在的TODs似乎取决于除基因多态性之外的其他因素的组合。
