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We tested the hypotheses that anglotensm-convertmg enzyme msertlon/deletlon (I/D) and anglotensmogen 235 methlomne/threomne (M/T) substitution gene polymorphisms mfluence anglotensm-converting enzyme and anglotensmogen serum concentrations and cardiac dimensions m 91 monozygotlc and 4 1 dlzygotlc twm pairs Cardiac dlmenslons were determined echocardlographlcally Anglotensm-converting enzyme levels were 242 11,43f. 18, and 58+-24 U/L for the II, ID, and DD genotypes, respectively (P<.Ol)Posterior wall thickness was 8 121 3, 8.62 1 7, and 8 9+ 1.9 mm for these genotypes (P< 05) Anglotensm-converting enzyme levels were correlated with posterior wall thickness (r= 15, P< 05) The mtrapalr differences in anglotensm converting enzyme levels for monozygotlc, concordant dlzygotlc, and discordant dlzygotlc twins were 1 361-l 6, 1 8651 6, and 17 2524 3 U/L, respectively The anglotensmogen M/T genotypes exerted no influence on cardiac dimensions or on anglotensmogen concentrations The additive genetic effect on anglotensm-convertmg enzyme levels (0 49), on posterior wall thickness (0 26), and on septum thickness (0.37) was significant (P<.Ol), although shared and nonshared envlronmental effects were also identified Our data confirm the impressive effect that the anglotensm-converting enzyme D allele exerts on anglotensm-converting enzyme plasma levels Furthermore, our data also suggest that the anglotensm-converting enzyme gene locus IS pnmanly responsible for anglotensm-converting enzyme plasma levels. Our twm study also indicates that the anglotensm-convertmg enzyme gene locus IS genetlcally linked to posterior wall thickness. The correlation between anglotensm-converting enzyme levels and posterior wall thickness suggests that this effect 1s exerted by anglotensm-converting enzyme We were unable to demonstrate genetic linkage between the anglotensmogen gene locus and cardiac dimensions m this study (Hypertension. 1997;29[part 2]:165-170.) Key Words l genetics l twins l ACE polymorphisms l anglotensmogen polymorphisms l cardiac hypertrophy A diallehc polymorphtsm m the ACE gene, characterized by a D or I allele m the 16th mtron of the ACE gene, has been associated with differences m plasma ACE levels, as well as risk for myocardial mfarctlon and cardiac hypertrophy 1 Tlret et al* used evidence from combined segregation and linkage analysis and showed that the I allele was characterized by lower ACE levels. A stmilar associatton between the I and D alleles and ACE m monocytes has also been tdenttfied 3 Cambten et a14 relied on an assoctation study, m which the DD genotype was associated with myocardial infarction m men with low risk They found that m that group, ACE levels did not decrease with age and were higher m patients with the DD and ID genotypes than m control SubJects Schunkert et a15 reported an excess homozygostty for the D allele among SubJects with cardiac hypertrophy as assessed by electrocardtographtc crttena. The D allele has also been associated with the severtty of cardiac hypertrophy m patie...

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Foreign DNA can integrate into the genomes of mammalian cells, and this process plays major roles in viral oncogenesis and in the generation of transgenic organisms and will be important in evolving regimens for human somatic gene therapy. In the present study, the insertion sites of adenovirus type 12 (Ad12) DNA genomes have been analyzed in detail in the Ad12-transformed hamster cell line T637, its revertants, which have lost most of the >20 Ad12 genome equivalents integrated chromosomally in cell line T637, and in the Ad12-induced tumor T191. Some of these junction sites have been molecularly cloned, and the nucleotide sequences at the sites of transition between viral and cellular DNAs have been determined. The sites of linkage between the hamster cellular and the foreign (viral) DNA are characterized by the frequent occurrence of patch homologies between the recombination partners. The cellular junction sites investigated here are not transcriptionally active. One of the cellular DNA sequences abutting the right Ad12 DNA terminus in cell line T637 (os2) is represented only once in the hamster genome and has a strikingly low abundance of 5-CG-3 dinucleotide sequences. One 5-GCGC-3 sequence close to the Ad12 DNA integration site is heavily methylated in normal cells, Ad12-transformed cells, and Ad12-induced tumor cells. The second such sequence is more remote from the junction site, is partly methylated in BHK21 hamster cells, and shows differences in methylation in different Ad12-transformed cell lines. This site is unmethylated in liver DNA. The cellular DNA sequence at the site of Ad12 linkage in the tumor T191 exhibits homologies to highly repetitive sequences of the Alu family and to an origin of hamster DNA replication containing an Alu element. A number of junction sites between Ad12 DNA and hamster or mouse DNA in Ad12-transformed cell lines or Ad12-induced tumor cell lines, investigated here and previously, are characterized by stem-loop structures encompassing the junction sites.