Adiponectin ‐11377C/G and +276G/T Polymorphisms affect Adiponectin Levels but do not Modify Responsiveness to Therapy in Resistant Hypertension

Abstract

Resistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity. Low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated with RHTN. Single nucleotide polymorphisms (SNPs) -11377C/G (rs266729) and +276G/T (rs1501299) in ADIPOQ (adiponectin gene) were associated with hypertension. This study evaluated the association between two SNPs (-11377C/G and +276G/T) and adiponectin levels in RHTN. This study comprised 109 patients with RHTN genotyped for both polymorphisms. A cross-sectional study was designed to compare features of CC homozygous versus G allele carriers for -11377C/G and GG homozygous versus T allele carriers for +276G/T. Office and ambulatory BP measurements were similar among genotypes subgroups in both SNPs as well as the markers of target organ damage (arterial stiffness, left ventricular mass index and microalbuminuria). Adiponectin concentrations were significantly higher in CC compared to G carrier for -11377C/G (CC:7.0 (4.0-10.2) versus 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) versus 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 analyses revealed that the minor alleles G (b-coefficient= -0.14, SE=0.07, p = 0.03) and T (b-coefficient=0.12, SE=0

Metabolic Syndrome-Related Features in Controlled and Resistant Hypertensive Subjects

“…Previous studies have shown an inverse association between adiponectin levels and low-grade albuminuria in essential 19 and resistant hypertensive patients. 20 , 21 Similarly in experimental studies, adiponectin knockout rats have higher levels of albuminuria (twice above normal values), and after replacement of the protein, albuminuria returned to its normal levels. 22 Hyperleptinemia is also an independent risk factor for coronary artery disease 23 and strong predictor of acute myocardial infarction.…”

The association of two polymorphisms in adiponectin-encoding gene with hypertension risk and the changes of circulating adiponectin and blood pressure: A meta-analysis

“…After rigorous literature search, a total of 41 articles were found, wherein 12 articles were qualified for the current meta-analysis [10–14, 16–22]. Out of 12 qualified articles, 8 articles including 12 independent studies (3358 cases and 5121 controls) compared genetic data on T45G and/or G276T polymorphisms between hypertensive and normotensive subjects [12–14, 16–19, 21], and 7 articles including 11 independent studies (3053 subjects) compared mean values of circulating adiponectin and/or blood pressure across the genotypes of polymorphisms under study [10–12, 14, 16, 20, 22].…”

Single nucleotide polymorphism creating a variable upstream open reading frame regulates glucocorticoid receptor expression

“…It is still a matter of debate if and to which extent such a protein reduction translates into a clinically significant effect (Johnson et al, 2011). Most polymorphisms involved in multifactorial disorders are likely to confer only small risks (de Faria et al, 2014;Wang et al, 2014;Zakharyan et al, 2014). Clinically relevant effects are therefore only seen if variants in several or even many genes work together (Wong et al, 2012;Bronkhorst et al, 2013).…”