Genetic determinants of plasma ACE and renin activity in young normotensive twins

Objective We investigated the determinants of plasma renin activity (PRA) a nd plasma levels of angiotensin-coverting enzyme (pACE), including the effe ct of the D/I polymorphism of the angiotensin-converting enzyme (ACE) gene, in monozygotic (MZ) and dizygotic (DZ) twins. Methods Sixty-nine pairs of twins underwent measurements of blood pressure, pACE and ACE D/I genotyping, In addition, in 30 pairs ambulatory blood pre ssure (ABP) monitoring was carried out. To ascertain twin's zygosity, some highly discriminating variable number of tandem repeats micro- and mini-sat ellite systems were analysed by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis and silver staining. The D/I polymorphi sm was assessed by PCR; pACE was measured in triplicate with a colorimetric assay, and PRA by a commercial kit In DZ twins, identity by descent of the D/I alleles was examined by PCR amplification of a highly polymorphic simp le sequence repeat at the human growth hormone gene. Results pACE levels were significantly (P < 0.01) higher in DD (9.27 +/- 2. 60 IU/I, mean a SD) than in II (6.68 +/- 3.0), with DI having intermediate levels (7.93 +/- 2.7). No difference of PRA between different D/I genotypes was found. Twin data analysis showed a statistically significant heritabil ity of pACE, but not of PRA, No differences between MZ and DZ twins in PRA, pACE and the relationship of the D/I genotype with pACE was found. Besides showing that the D/I genotype was the most important predictor of pACE, a multivariate analysis demonstrated that identity by descent of the D/I alle le, as assessed by growth hormone (GH) genotyping, also significantly affec ted pACE. Conclusions In this study of normotensive twins, pACE and not PRA showed si gnificant heritability, the former being tightly associated with the D/I AC E gene polymorphism, and/or with a quantitative trait locus in linkage dise quilibrium with it. J Hypertens 1999, 17:647-655 (C) Lippincott Williams & Wilkins.