An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

Abstract

A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 2993±49, 392.6±66.8, and 494.1±883 ,g/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval. (J. Clin. Invest. 1990Invest. . 86:1343Invest. -1346

The lack of association between angiotensin‐converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis

“…Since the homozygous ACE‐DD genotype is associated with tissue and plasma enzyme levels almost twice that of the homozygous ACE‐II genotype (Rigat et al., 1990), we initially speculated that individuals with the ACE‐DD genotype might release dopamine at higher levels and consequently could be more vulnerable to nicotine dependence. However, our results demonstrating no significant influence of the ACE‐I/D polymorphism on either smoking risk or the severity of nicotine dependence (Tables 2 and 3) do not argue in favor of our speculation.…”

“…Genotyping was performed by polymerase chain reaction (PCR) analysis using protocols previously described (Rigat et al., 1990). To exclude mistyping of the ACE‐ID heterozygotes as ACE‐DD homozygotes, all ACE‐DD genotype samples were additionally confirmed with insertion‐specific PCR (Shanmugam, Sell, & Saha, 1993).…”

“…A functional 287‐nucleotide fragment insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene accounts for approximately 50% of ACE levels (Rigat et al., 1990), is the most studied RAS‐related polymorphic variant, and is the only RAS‐related polymorphism investigated in the etiology of nicotine dependence so far (Baghai et al., 2008; Hubacek et al., 2001, 2004). Although significantly greater risk for being a smoker has been observed among ACE‐DD homozygous individuals with depression in the German population (Baghai et al., 2008), studies comprising healthy subjects from the Czech Republic and German populations found no association between the ACE‐I/D polymorphism and smoking risk (Baghai et al., 2008; Hubacek et al., 2004).…”

Association of polymorphisms of the renin–angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough

“…(1) ACE I/D polymorphism: The I/D polymorphism of the ACE gene was identified by polymerase chain reaction (PCR) using a set of oligonucleotide primers flanking the polymorphic site according to the method described by Rigat et al 15 A set of primers was designed to encompass the polymorphic region in intron 16 of the ACE gene (sense primer 5 0 -CTGGAGACCACTCCCATCCTTTCT-3 0 and anti-sense primer 5 0 -GATGTGGCCATCA-CATTCGTCAGAT-3 0 ). The PCR reaction mixture contained 100 ng of the DNA template, 5 pmol/ml of each primer, 1 ml of 2 mmol/L DNTP, 1 ml of 5% DMSO, 0.04 ml of ampli Taq DNA polymerase, and 2 ml of PCR buffer.…”

Interactions between five candidate genes and antihypertensive drug therapy on blood pressure

“…Plasma AGT is significantly elevated in patients with the AGT T235 allele, 4 and serum ACE is significantly higher in subjects with the ACE D allele. 5 Candidate genes related to other blood pressure regulating systems are a-adducin (ADD1) and b3-subunit of G-protein (GNB3). ADD1 may affect blood pressure by modulating renal tubular reabsorption of sodium through the activation of Na þ , K þ -ATPase (adenosine triphosphatase) with the 460W allele exhibiting higher affinity for the Na þ , K þ -ATPase pump.…”