Angiotensinogen (AGT) M235T, AGT T174M and Angiotensin-1-Converting Enzyme (ACE) I/D Gene Polymorphisms in Essential Hypertension: Effects on Ramipril Efficacy.

BACKGROUND: Hypertension, one of the most important risk factors for premature cardiovascular disease, is a major worldwide public health problem. Angiotensin-1-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms are thought to be associated with primary hypertension. In the present study, we examined the frequency of these gene polymorphisms in an adult population with and without essential hypertension. Furthermore, we evaluated the effect of ACE and AGT gene polymorphisms on ramipril treatment efficacy in the hypertensive patients. METHODS: A total of 166 adults (83 hypertensives and 83 normotensives) were involved in the study and genotyped for AGTM235T (rs699), AGTT174M (rs4762) and ACEI/D (rs1799752) gene polymorphisms. RESULTS: The genotype and allele distribution of the AGTM235T variant significantly differed between hypertensives and normotensives [odds ratio (OR) = 1.57% (T vs M allele), 95% confidence intervals (CIs): 1.01 - 2.44; p=0.045 for hypertensives]. However, none of the 3 studied Simple Nucleotide Polymorphisms were associated with the blood pressure-lowering response to ramipril. CONCLUSION: These results suggest that AGTM235T gene polymorphism is associated with essential hypertension. However, none of the AGTM235T, AGTT174M and ACEI/D gene polymorphisms influenced ramipril effectiveness.

The frequency of 4 common gene polymorphisms in nonagenarians, centenarians, and average life span individuals.

Single nucleotide polymorphisms of angiotensin-converting enzyme (ACE) such as rs1799752, nuclear factor kappa B (NFkB) such as rs28362491 and cholesteryl ester transport protein (CETP) such as rs708272 (TaqB1) and rs5882 (I405V) were evaluated in nonagenarians, centenarians, and average life span individuals (controls). The study population (n = 307; 190 nonagenarians, 12 centenarians and 105 middle-aged controls) was genotyped for ACE, NFkB, and CETP genetic variants. The age of nonagenarian and centenarian group ranged between 90 and 111 years; centenarians and controls age ranged from 99 to 111, and from 18 to 80 years, respectively. The I carriers of ACE I/D gene were fewer in nonagenarians compared to centenarians (37.6% vs 62.5%, P = .016). The I carriers of ACE gene were more frequent in centenarians compared to controls (62% vs 41%, P = .045). No differences in frequency of common NFkB and CETP genotypes between patients with exceptional longevity and middle-aged patients were observed.

Cholesteryl ester transfer protein and ATP-binding cassette transporter A1 genotype alter the atorvastatin and simvastatin efficacy: time for genotype-guided therapy?

We compared the efficacy of atorvastatin with simvastatin according to cholesteryl ester transfer protein (CETP) and adenosine triphosphate-binding cassette transporter A1 (ABCA1) genes. Patients treated with atorvastatin (n = 254) or simvastatin (n = 332) were genotyped for CETP (TaqIB and I405V) and ABCA1 (R219K) genetic variants. For genotype B1B2, atorvastatin compared with simvastatin treatment resulted in a greater decrease in total cholesterol (35.4% vs 31.6%, P = .035) and a lower increase in high-density lipoprotein cholesterol (2% vs 8%, P = .05). For genotype B2B2, atorvastatin compared with simvastatin treatment resulted in a lower decrease in low-density lipoprotein cholesterol (31.85 vs 42%, P = .029). For genotypes RR and KK, atorvastatin compared with simvastatin treatment resulted in a greater decrease of triglycerides (27% vs 17% and 35% vs 15%, respectively; P = .02 for all comparisons). The TaqIB and R219K (opposite to I405V) gene polymorphisms seem to modify the response to lipid-lowering therapy with simvastatin or atorvastatin treatment.