Polymorphisms of the TGFBRAP1 gene in relation to blood pressure variability and plasma TGF-β1.

TGF-β receptor-associated protein 1 (TGFBRAP1), as a chaperone, binds Smad4 to participate in vascular development and remodeling which is closely related to the aetiology of essential hypertension (EH). Herein, the main aim of this study is to investigate the genetic susceptibility of TGFBRAP1 to hypertension. A case-control study comprising 2012 hypertension cases and 2210 controls was used to generate the hypothesis of the association of TGFBRAP1 gene with EH and another case-control study in a children population then proceeds to further replicate the association. Logistic regression model was used to adjust confounding factor for EH and general linear model (GLM) was applied to compare blood pressure levels and plasma TGF-β1 levels between genotypes in cases and controls. There was no statistical association with EH after the covariates were controlled for. However, quantitative trait analysis indicated that DBP had a linear decrease with the variations of rs2679860 (p = 0.005) after adjustment for confounding factor but the direction of this genetic effect was opposite of that in the children population. And normally distributed square root of TGF-β1 (pg/ml) had a linear increased with the variations of rs2679860 (p = 0.042) after adjusting covariates. Our finding supports the association of rs2679860 polymorphisms of TGFBRAP1 and DBP variation as well as plasma levels of TGF-β1 and that suggests the variation of rs2679860 might influence the direct modulatory effect of TGF-β1 on the blood pressure by regulating the plasma levels of TGF-β1.

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