Ace Gene Polymorphisms

The most widely studied polymorphism of the ACE gene is based on the presence (insertion, I) or absence (deletion, D) of a 287-base-pair element in intron 16.[6] Although the intraindividual plasma level of ACE is rather stable, the prominent interindividual variation has been linked to this I/D polymorphism,1-6-1 which accounts for 47% of the phenotypic variance in healthy individuals. It has been shown that Caucasian subjects with

ACE-DD genotype have the highest, subjects with ID genotype intermediate, and subjects with II genotype have the lowest concentrations. These findings have been confirmed in diverse populations including French centenarians,[7] Pima Indians,[8] and whites in the United States.[9] However, they could not be replicated for African-Americans, suggesting an important role for ethnic background.[9]

The ACE gene I/D polymorphism genotyping method originally published by Rigat et al.[6] results in a preferential amplification of the D allele with a possible mistyping of approximately 5% of ID heterozygotes as DD homozygotes.[10] One better technique is to use a second pair of primers, which are located inside the insertion-specific sequence as proposed by Lindpaintner et al.[10] Another improved method has been published by Evans et al.[11] and Ueda et al.[12] They used a third primer located in the insertion element that was added to the reaction cocktail together with the first set of primers. Addition of 5% DMSO and the application of a ''hotstart'' (i.e., initial heating at 95°C and using of wax platelets in the PCR tubes) procedure highly improved the specificity of the original protocol.

PHARMACOGENETIC IMPLICATIONS OF ACE GENOTYPING: STUDIES IN ESSENTIAL HYPERTENSION AND CARDIOVASCULAR DISEASE

In patients with essential hypertension, the ACE gene polymorphism and the response to treatment with ACE inhibitors was subject to research in several clinical trials (Table 1). Hingorani et al.[13] and Dudley et al.[14] could not describe any correlation between blood pressure response to an ACE inhibitor and ACE genotype in individuals with essential hypertension. Nakano et al.[15] reported that blood pressure response to a single dose of 50 mg captropril does not correlate with ACE genotype but rather with plasma renin activity. Stavroulakis et al.[16] showed that after treatment with fosinopril, blood pressure reduction was significantly greater in DD

Angiotensinogen (liver)

Renin (kidney)

ACE inhibitors

Angiotensin I (decapeptide)

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook


Post a comment