科研之友
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摘要
NEDD4L is involved in the regulation of plasma volume and blood pressure by controlling cell surface expression of the kidney epithelial Na+ channel. Previously, the cryptic splice variant rs4149601(G/A) A allele of NEDD4L, generating isoform I, was estimated to decrease blood pressure by downregulating Na+ reabsorption. However, a recent functional study showed that isoform I should lead to abnormal Na+ reabsorption increases by antagonistically downregulating epithelial Na+ channel activities. To determine whether the variant rs4149601 A allele is a risk factor for hypertension, has an impact on the antihypertensive response to hydrochlorothiazide, and is associated with orthostatic hypotension, we performed a case-control study of hypertension (n = 1686), a 4-week clinical trial (n = 542), and a case-control study of orthostatic hypotension (n = 793) in Chinese subjects. We found that the A allele was significantly associated with hypertension after appropriate adjustment (odds ratio: 1.39; 95% CI: 1.13 to 1.72; P = 0.002). The blood pressure reduction in A carriers after hydrochlorothiazide treatment was greater than that in GG carriers, with differences of 6.1 mm Hg (P = 0.009) in systolic blood pressure and 2.7 mm Hg (P = 0.027) in diastolic blood pressure. The A allele was significantly associated with orthostatic hypotension after adjustment for cardiovascular risk factors (odds ratio: 0.68; 95% CI: 0.48 to 0.98; P = 0.039). In conclusion, rs4149601 is a genetic risk factor for hypertension and a protective factor against orthostatic hypotension in hypertensive subjects, and the antihypertensive response to hydrochlorothiazide is more sensitive in A allele carriers than in GG carriers. Consequently, the A allele may be a useful marker for predicting hypertension, orthostatic hypotension, and antihypertensive response to hydrochlorothiazide. (Hypertension. 2009; 54: 796-801.)
- 出版日期2009-10
- 单位中国医学科学院阜外医院; 中国医学科学院北京协和医院
