Polymorphism of the angiotensin I converting enzyme gene in essential hypertensive patients.

Insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene has been associated with ischemic heart disease and hypertension. The D allele reportedly correlates with myocardial infarction and it has been suggested that it may serve as the basis of population-based risk assessment. Similarly, determining whether there is an ACE allele pattern associated with hypertension could be useful in developing screening strategies. Previous reports have not shown consistent findings in Caucasian and Japanese population groups, some having a predominance of the I allele. Although African Americans have the highest prevalence of hypertension in the world, their ACE gene polymorphism frequencies have not been clearly defined. We studied the allele and genotype frequencies in this group, consisting of 133 essential hypertensive subjects, and compared their findings with those reported from normotensive African Americans and from other racial groups. The black patients had a different allele distribution than the other populations in that the D was more common than the I allele, occurring at a rate of 59.7%. The most common genotype was DD and it was present in 42.5% of the hypertensive subjects in contrast to the ID genotype which was the most commonly reported genotype in normotensive individuals. The genotype pattern (frequencies of II, ID, DD) was significantly different (p < 0.005, 2 df) from Japanese and Caucasian (Scotland and Australia) populations. There was no common allele or genotype distribution amongst these diverse hypertensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequencies of the angiotensinogen gene and angiotensin I converting enzyme (ACE) gene polymorphisms in African Americans.

The purpose of the present study was to characterize three polymorphisms within the renin-angiotensin-aldosterone system in an African American population. A new mispairing primer polymerase chain reaction (PCR) was developed to identify two polymorphisms (T174M, M235T) in the angiotensinogen gene. A previously described PCR method was used to identify an insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene. Forty healthy, unrelated African Americans participated. The T174M mutation occurs less frequently (5.0%) than the M235T mutation (87.5%). The ACE D polymorphism occurs at a higher rate (70%) than the I. The data reveals that the two angiotensinogen mutation allele frequencies occur at similar rates regardless of the ACE gene allele. There appears to be no association between the mutations, indicating the loci are not linked.

Cloning of the rat edg-1 immediate-early gene: expression pattern suggests diverse functions.

The edg-1 immediate-early gene encodes a G-protein-coupled receptor homolog implicated in endothelial cell differentiation. We report the cloning of the rat edg-1 gene. Our Northern analyses indicate that edg-1 is much more widely expressed than previously thought. edg-1 mRNA was found in many organs at several stages of development with relatively high levels present in adult brain. edg-1 transcripts were also detected in several cell lines. Expression of edg-1 mRNA in the PC12 cell model of neuronal differentiation was unaffected by agents that cause PC12 cells to differentiate or proliferate. Therefore, edg-1 may play a cell-type-specific role in differentiation and also participate in neurotransmission.

Analysis of two variants of the angiotensinogen gene in essential hypertensive African-Americans.

Two mutations (T174M and M235T) in the angiotensinogen gene have been reported to be associated with hypertension. This study examines the frequency of these mutations among African-American hypertensive patients (n = 109). The allele frequency of the T174M mutation was 4.6% and the frequency of the M235T mutation was 86.7%. The genotypic frequencies agreed with the conditioned Hardy-Weinberg predictions based on allele frequencies. The homozygote wild-type genotype at the T174 site was more frequent than the mutation and occurred at a rate of 91.7%. Conversely, the homozygote for the mutation at the M235 site was more frequent and occurred at a rate of 75.2%. Mutation frequencies for T174M and M235T in this African-American population differ from those previously reported from a white hypertensive population (P = .0058 and P = .0001, respectively). In summary, the representation of the angiotensinogen allele frequencies differ among hypertensive populations.

Cloning and characterization of a putative G-protein coupled receptor potentially involved in development.

Polymerase chain reaction techniques and medium stringency library screening were used to isolate a rat cDNA ("H218") which encodes a novel guanine nucleotide-binding protein coupled receptor homolog ("pH218"). Northern analysis revealed that brain H218 mRNA is preferentially expressed during embryogenesis. In addition, H218 mRNA is expressed in all developing tissues and rodent cell lines examined with highest levels detected in primitive, transformed cells. H218 mRNA expression in cell lines is rapidly increased by a tumor promoter and rapidly decreased by a differentiation-inducing growth factor. Finally, all of the sequence motifs characteristic of Src homology 2 domains are present in pH218 but in a unique arrangement. We conclude that pH218 may function as a growth factor receptor.