Essential Hypertension Risk Factors: Serum Uric Acid, Hsd3b1 Gene Polymorphism

Background and aims: Hyperuricemia has long been known to be associated with cardiovascular disease, and it is particularly common in people with hypertension, metabolic syndrome, or kidney disease. Most authorities have viewed elevated uric acid as a secondary phenomenon that is either innocuous or perhaps even beneficial, since uric acid can be an antioxidant. However, recent experiments have challenged this viewpoint. In this paper we assess the relationships of serum uric acid (SUA) to 4-year hypertension incidence, and argue that uric acid is a true risk factor for hypertension.Methods: In 2000, 5843 participants aged 18-54 at baseline survey were non-hypertensive (＜135/85mmHg). In 2004, 4688 (3115 men, 1573 women) were reexamined. Hypertension incidence of the cohort was calculated.Results: Age-standardized hypertension incidence (SBP＞=140 or DBP>=90 or using antihypertensive drugs in the last two weeks) was 13.0% (men: 16.9%; women: 9.1%). For both gender, hypertension incidence was higher with higher SUA quartile (P＜0.05). The RR comparing the highest with lowest quartile of SUA were 2.14 (95% confidence interval [CI]: 1.63-2.81) in men and 2.11 (95% CI: 1.27-3.50) in women. After adjustment of baseline SBP, DBP, the level of fasting glucose, TC, HDL-C, TG, lipid- lowering medication use, BMI, alcohol, smoking and this SUA- hypertension relationship in male was attenuated but remained statistically significant (RR-1.60, 95% CI: 1.19-2.16). Age- standardized hypertension incidence in male was higher (RR=2.42, 95% CI: 1.53-3.81) with higher increase of SUA (≥P75).Conclusion: These data indicate that SUA is a risk factor for hypertension incidence that is independent of the level of fasting glucose, TC, HDL-C, TG, lipid-lowering medication use, BMI, smoking, and alcohol intake. A 4-year increase of SUA is associated with significantly greater risk of hypertension in men. Background and aims: There has been recent interest in HSD3B1 because of the essential role of hydroxysteroid dehydrogenase 3β1 in the biosynthesis of steroid hormones including aldosterone. It has been proposed that genetic variation in HSD3B1 could lead to an elevation in plasma aldosterone, with resultant increase in intravascular volume and HT. We hypothesized HSD3B1 genetic variations could confer high risk of hypertension and predict blood pressure response to hydrochlorothiazide.Methods: One case control study was performed to test the association of single nucleotide polymorphisms of HSD3B1 with hypertension (286 cases vs. 316 controls). A total of 286 untreated hypertensive patients were to hydrochlorothiazide sustained release treatments for 8 weeks to determine the association of blood pressure response with HSD3B1 rs1047303.Results: We did not find an association of HSD3B1 rs1047303 with hypertension in both men and women. HSD3B1 AC genotype male carriers had 8.8 mmHg lower reduction in systolic blood pressure response to hydrochlorothiazide than did AA genotype male carriers after adjusting for age, pretreatment blood pressure, body mass index and fasting plasma glucose (P=0.036).Conclusions: HSD3B1 variant is not associated with hypertension, but can predict systolic blood pressure responses to hydrochlorothiazide in men.