Abstract
Arterial stiffness is an important factor in hypertension. Fibulin 2 is an extracellular matrix scaffold protein involved in arterial stiffness and, hence, the fibulin 2 (FBLN2) gene may be a candidate for hypertension susceptibility. 4 single nucleotide polymorphisms (SNPs) of FBLN2 were evaluated in an association case-control study containing 447 hypertensive patients and 344 normotensive control subjects. The minor allele frequencies of rs3732666 and rs1061376 were significantly lower in hypertensives. The odds ratios (OR) for having the protective G (rs3732666) and T (rs1061376) alleles were 0.75 (95%CI: 0.58 to 0.96) and 0.83 (95%CI: 0.66 to 1.02), respectively. For rs3732666, the OR for hypertension in AG+GG subjects, compared with AA, was 0.71 (95%CI: 0.52 to 0.95). The protective genotype AG+GG was associated with significantly lower systolic blood pressure (SBP) [−3.6 mmHg (P = 0.048)]. There was a significant age interaction with rs3732666; the effect decreasing with increasing age. For rs1061376, TT subjects had an OR for hypertension of 0.53 (95%CI: 0.32 to 0.87) compared with CC subjects, with reduced SBP (−7.91 mmHg; P = 0.008) and diastolic BP (DBP) (−3.69 mmHg; P = 0.015). The presence of a G allele was an independent predictor of intima-media thickness (IMT); G carrier’s having lower mean IMT (−0.037 mm, P = 0.027) compared with AA. Our results provide the first evidence for FBLN2 as a new gene associated with hypertension.
Highlights
Increases in systolic and diastolic blood pressure (SBP and diastolic BP (DBP), respectively) contribute to millions of deaths worldwide every year due to coronary heart disease, stroke, and other vascular diseases [1,2]
Based on the postulated role of fibulin 2 in the remodeling and elasticity of the vascular wall, we tested the hypothesis that fibulin 2 may be involved in regulation of blood pressure and, may be a susceptibility gene for essential hypertension and, we have shown that variations in FBLN2 gene are associated with reduced levels of systolic blood pressure (SBP) and decreased risk of hypertension
For rs3732666, the minor allele frequency (MAF) was significantly lower in hypertensive patients than in control subjects (0.19 vs. 0.24; p = 0.022) with an odds ratio (OR) for having the protective allele (G) of 0.75 (95%CI: 0.58 to 0.96; p = 0.022)
Summary
Increases in systolic and diastolic blood pressure (SBP and DBP, respectively) contribute to millions of deaths worldwide every year due to coronary heart disease, stroke, and other vascular diseases [1,2]. Pharmacological treatment to lower blood pressure markedly reduces the risk of an adverse cardiovascular event, stroke, in hypertensive individuals [3,4]. Genetic and environmental factors combine in determining the arterial tone and blood pressure [5,6]. Knowledge of pathways involved in cardiovascular structure and function together with the candidate gene linkage approach, has identified many genes associated with increased arterial stiffness and high blood pressure [10]. The direct clinical value of such genetic association studies continues to be debated [13] but, identifying contributory genes does advance the understanding of blood pressure regulation and enables vulnerable individuals to be identified so that a better strategy of prevention and treatment of hypertension may be implemented
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