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Byline: Joyita. Banerjee, Abhishek. Gupta, Vertica. Agnihotri, Rashmita. Pradhan, Ramesh. Kandel, Ashish. Upadhyay, Sadanand. Dwivedi, Lalit. Kumar, Sharmistha. Dey, Aparajit. Dey Background: rs4340ID polymorphism of angiotensin-converting enzyme (ACE) correlates with [...]

The Angiotensin-converting enzyme (Ance) gene of Drosophila melanogaster is a homologue of mammalian angiotensin-converting enzyme (ACE), a peptidyl dipeptidase implicated in regulation of blood pressure and male fertility. In Drosophila, Ance protein is present in vesicular structures within spermatocytes and immature spermatids. It is also present within the lumen of the testis and the waste bag, and is associated with the surface of elongated spermatid bundles. Ance mRNA is found mainly in large primary spermatocytes and is not detectable in cyst cells. Testes lacking germ cells have reduced levels of ACE activity, and no Ance protein is detectable by immunocytochemistry, indicating that the germ cells are the major site of Ance synthesis. Ance mutant testes lack individualised sperm and have very few actin-based individualisation complexes. Spermatid nuclei undergo scattering along the cyst and have abnormal morphology, similar to other individualisation mutants. Mutant spermatids also have abnormal ultrastructure with grossly defective mitochondrial derivatives. The failure of Ance mutant testes to form individualisation complexes may be due to a failure in correct spermatid differentiation. Taken together, the expression pattern and mutant phenotype suggest that Ance is required for spermatid differentiation, probably through the processing of a regulatory peptide synthesised within the developing cyst. Keywords: Ance; Metallopeptidase; Spermatogenesis; ACE; Spermatid individualisation

Testis angiotensin-converting enzyme (ACE) is a unique form of ACE, only produced by male germ cells, and results from a testis-specific promoter found within the ACE gene. We have investigated the role of cAMP-response element modulator (CREM)[Tau] in testis ACE transcription. In gel shift experiments, testes nuclear proteins retard an oligonucleotide containing the cAMP-response element (CRE) found at position -55 in the testis ACE promoter. Anti-CREM antibody supershifts this complex. Competitive gel shift shows that recombinant CREM[Tau] protein and testes nuclear proteins have a similar specificity of binding to the testis ACE CRE. Functional analysis using in vitro transcription and transfection studies also demonstrate that CREM[Tau] protein is a transcriptional activator of the testis ACE promoter. Western blot analysis identifies CREM[Tau] protein in the protein-DNA complex formed between nuclear proteins and the testis ACE CRE motif. This analysis also identified other CREM isoforms in the gel-shifted complex, which are thought to be CREM[Tau]1/2, CREM[Alpha]/[Beta], and S-CREM. These data indicate that CREM[Tau] isoforms play an important role as a positive regulator in the tissue-specific expression of testis ACE.

The DD genotype linked with higher concentrations of circulating angiotensin-converting enzyme (ACE) occurs more often among myocardial infarction patients with low-body mass index and low plasma levels of ApoB than among controls. This indicates that the ACE/ID polymorphism is a powerful risk factor both for myocardial infarction and for coronary heart disease in general. This new risk factor will apply to many people once thought to be in little danger of developing heart problems.

The dcp gene isolated from plasmids pBR328 library of Salmonella chromosomal DNA was cloned, sequenced, and its messenger RNA (mRNA) analyzed to characterize the gene. The gene consists of a 2.8 kilobase region with an open reading frame for a 77,269 kilodalton protein corresponding to dipeptidyl carboxypeptidase as determined by electrophoresis and gel filtration. mRNA analysis revealed that the gene is not cotranscribed with any other gene. The amino acid sequence deduced from the nucleotide sequence bears a striking similarity to a peptidase coded for by the opdA gene.

Polymorphisms at the apolipoprotein B (APOB XbaI, EcoRI, insertion-deletion), apolipoprotein E (APOE), and angiotensin-converting enzyme (ACE) loci are thought to be involved in susceptibility to coronary artery disease (CAD) and myocardial infarction. The aim of this study was to determine whether the allele distribution of the APOB, APOE, and ACE polymorphisms is different in 2 Italian regions with higher (northern Italy) and lower (Sardinia) CAD occurrence. The frequencies of the APOB and APOE alleles that are considered CAD risk factors were higher in northern Italy (APOB X- = 0.655; APOB R = 0.198; APOB insertion = 0.757; APOE*4 = 0.110) than in Sardinia (APOB X- = 0.568; APOB R- = 0.159; APOB insertion = 0.680; APOE*4 = 0.052), although only APOE allele frequencies differed significantly (p = 0.001). ACE deletion allele frequencies in the 2 geographic areas showed an opposite pattern (northern Italy = 0.658; Sardinia = 0.721). Furthermore, we investigated the impact of APOB and APOE polymorphisms on interindividual variation in total cholesterol level in the 2 Italian samples, which differ in dietary habits. Only APOE phenotypes showed different mean levels of total cholesterol; the association was significant only in northern Italy (p = 0.04), where continental dietary habits and higher mean cholesterol levels prevail. These results support the suggestion that the cholesterol increasing effect of APOE*4 is environmentally mediated. Analysis of allele distributions among European populations, with remarkable differences in CAD prevalence, revealed a constant positive relationship between APOE*4 allele frequency and CAD incidence. The highest frequencies of APOB X- and R - were observed in Finland, where the incidence of CAD is high, and there is a partial agreement between APOB R- frequency and CAD occurrence across Europe, while APOB insertion and ACE deletion alleles are evenly distributed among European populations. KEY WORDS: CORONARY ARTERY DISEASE, APOB, APOE, ACE, ITALY, EUROPE, Polymorphic variants of several genes, for example, apolipoprotein B (APOB), apolipoprotein E (APOE), and angiotensin-converting enzyme (ACE), are thought to be involved in susceptibility to coronary artery disease (CAD). Apolipoprotein [...]

Most medical researchers believe that high blood pressure (hypertension) is a complex trait that arises from the interplay of a wide variety of genetic and environmental factors. Hypertension is a common problem; in many industrialized countries about one quarter of all adults have this significant risk factor for heart attack, stroke, and kidney failure. Hypertension may result from different causes in different people. For example, some people appear genetically susceptible to hypertension induced by excess sodium intake, while others can consume large amounts of dietary salt without developing a problem. This heterogeneity of hypertension among people makes it especially difficult to identify the various causes of hypertension from the data on human patients. Much research with large numbers of subjects has concentrated on rats, in which the contribution of genetics to hypertension has been examined. Researchers have identified two genes that figure prominently in the development of hypertension in a strain of rats that is spontaneously prone to strokes. One of these genes, BP/SP-1, appears to be located in the same region as rat chromosome 10 as is the angiotensin converting enzyme (ACE). It is not yet certain that BP/SP-1 and the ACE gene are identical; additional research using techniques of molecular biology will be required to verify this. The involvement of the ACE gene seems very plausible because of the important role played by ACE in the regulation of blood pressure. Furthermore, in some human patients, inhibitors of ACE have been very effective in lowering blood pressure. However, enthusiasm for these genetic findings should be tempered. In the past, attempts to find the genetic basis for complex diseases have proven to be more difficult than initially anticipated by researchers. In some disorders, one gene accounts for much of the observed variability in the trait of interest. However, genetic research becomes more complex when several genes contribute to a trait, which may be the case in hypertension. (Consumer Summary produced by Reliance Medical Information, Inc.)