Adiponectin polymorphisms -11377G/T and +276G/T are associated with adiponectin levels in resistant hypertension

Author(s)

Ana Paula Cabral de Faria Modolo

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2014-04-07

Examining board members

Heitor Moreno Junior; Jose Antonio Rocha Gontijo; Gabriel Forato Anhê; Marcelo Rizzatti Luizon; Heno Ferreira Lopes

• Advisor: Heitor Moreno Junior

Abstract

Background: Resistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity, and defined as high blood pressure (BP) maintained in spite of concurrent use of three or more antihypertensive drugs of different classes, combined at optimal doses and including a diuretic. Previous studies demonstrated that low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated with RHTN. Indeed, single-nucleotide polymorphisms (SNPs) rs266729 and rs1501299 in adiponectin coding gene ADIPOQ were associated with hypertension and risk of cardiovascular disease. This study evaluated the association between two of the most widely studied SNPs (-11377C/G and +276G/T) and adiponectin plasma levels in RHTN subjects. Design and Methods: This study comprised 109 RH patients genotyped for both polymorphisms by Real-time Polymerase Chain Reaction (PCR) method using fluorescent probes. We conducted a cross-sectional design comparing clinical and laboratorial characteristics of CC homozygous (n=56) vs. G allele carriers (n=53) for -11377C/G and GG homozygous (n=49) vs. T allele carriers (n=60) for +276G/T. Adiponectin levels were measured by enzyme-linked immunoassay. Results: Office and ambulatory BP measurements were similar among genotypes subgroups in both SNPs as well as the markers of target organ damage. Adiponectin levels were significantly higher in CC compared to G-carrier for -11377C/G (CC = 7.0 (4.0-10.2) vs. G allele = 5.5 (2.5-7.9), p=0.04) and lower in GG compared to T-carrier for +276G/T (GG = 5.3 (2.3-7.7) vs. T allele = 7.1 (3.6-10.5), p=0.04). Adjusting for systolic ambulatory BP, body mass index, age, gender, race and presence of type 2 diabetes, multiple linear regression revealed that the minor alleles G (beta coefficient = -0.16, SE = 0.07, p = 0.02) and T (beta coefficient = 0.12, SE = 0.06, p = 0.04) were independent predictors of adiponectin levels. Conclusion: The -1377C/G and +276G/T polymorphisms in ADIPOQ were associated with adiponectin levels in RH subjects (AU)

• FAPESP's process: 11/19431-6 - Role of aldosterone synthase and adiponectin polymorphisms on hemodynamic parameter and vascular stiffness in obese resistant hypertensives
• Grantee: Ana Paula Cabral de Faria Modolo
• Support Opportunities: Scholarships in Brazil - Doctorate