Journal
GENE
Volume 646, Issue -, Pages 129-135Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2017.12.023
Keywords
Metalloproteinases; Genetic polymorphism; Blood pressure; Target organ damage; Obesity; Refractory hypertension
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Funding
- Sao Paulo Research Foundation (FAPESP), SP, Brazil [2012/23608-1]
- National Council for Scientific and Technological Development (CNPq)
- Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil
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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 MMP2 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.
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