Renin Gene Polymorphisms and Haplotypes, Blood Pressure, and Responses to Renin-Angiotensin System Inhibition

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2007-08, Vol.50 (2), p.340-347
• Main Authors: Moore, Niamh, Dicker, Patrick, OʼBrien, John K, Stojanovic, Milos, Conroy, Ronán M, Treumann, Achim, OʼBrien, Eoin T, Fitzgerald, Desmond, Shields, Denis, Stanton, Alice V
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amides - therapeutic use; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure Monitoring, Ambulatory; Cardiology. Vascular system; Chi-Square Distribution; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Endocrine kidney. Renin-angiotensin-aldosterone system; Female; Follow-Up Studies; Fumarates - therapeutic use; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Haplotypes - genetics; Humans; Hypertension - diagnosis; Hypertension - drug therapy; Hypertension - genetics; Linear Models; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Multivariate Analysis; Polymorphism, Genetic; Renin - genetics; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - genetics; Severity of Illness Index; Treatment Outcome; Vertebrates: endocrinology
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.106.085563

Renin catalyzes the rate-limiting step of the renin-angiotensin system. A T allele variant at position −5312 within a distal enhancer region has been reported to increase in vitro renin gene transcription. Among 387 White bank employees, ambulatory blood pressures were higher in 133 −5312T allele carriers than in 254 CC homozygotes—mean differences [99% confidence interval] between carriers and homozygotes for daytime and night-time systolic/diastolic pressure were 2.5[0.4,4.6]/1.7[0.2,3.2] and 2.4[0.5,4.4]/1.5[0.1,2.9] respectively. Ambulatory pressure estimates for the only common renin haplotype including the −5312T variant (−5312T, 5090C, 5912A, 9479A, 10194G), were statistically significantly higher than estimates for all other haplotypes. Among 259 White hypertensive participants in a randomized double-blind clinical trial comparing a renin antagonist, aliskiren, with an angiotensin receptor blocker, losartan, plasma renin activity did not differ with renin −5312C/T genotype. Nocturnal blood pressure reductions with losartan 100 mg daily were significantly greater in −5312T allele carriers than in CC homozygotes (mean[standard error]; −12.9[3.7]/−7.9[2.4] versus −7.1[2.5]/−4.2[1.6]) whereas with aliskiren 150 and 300 mg daily, lesser reductions were observed in −5312T allele carriers than in CC homozygotes (−5.4[2.0]/−4.1[1.3] versus −10.1[1.4]/−6.5[1.1]; P