Two Loci Affect Angiotensin I–Converting Enzyme Activity in Baboons

Kammerer, Candace M.; Rainwater, David L.; Schneider, Jennifer L.; Cox, Laura A.; Mahaney, Michael C.; Rogers, Jeffrey; VandeBerg, Jane F.

doi:10.1161/01.hyp.0000046280.16849.bf

Cited by 7 publications

(12 citation statements)

References 28 publications

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“…4 The within-run and between-run coefficients of variation for this assay were 1.4% and 4.6%, respectively. ACE activities were transformed by natural logarithms before analysis to reduce skewness.…”

Section: Phenotypes and Genotypesmentioning

confidence: 80%

“…In addition, a genome scan of ACE activities in baboons did not reveal any QTLs for ACE activities on the baboon homologue of human chromosome 4q. 4 Several genome screens for QTLs influencing blood pressure have been performed in mice and rats, but a search of the mouse genome with the NCBI Map Viewer (http://www.ncbi.nlm.nih.gov/mapview/) revealed no blood pressure QTLs on mouse chromosomes 3 or 8, the regions that are homologous to human chromosome 4q (http:// www.ncbi.nlm.nih.gov/Homology/). In contrast, use of the Virtual Comparative Map tool from the Rat Genome Database revealed several blood pressure QTLs on rat chromosomes 2q, 16p12-14, and 19p12-q12, the regions that exhibit homology to human chromosome 4q (http://rgd.mcw.edu/ VCMAP/).…”

Section: Discussionmentioning

confidence: 99%

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Two Quantitative Trait Loci Affect ACE Activities in Mexican-Americans

et al. 2004

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Abstract-Angiotensin-converting enzyme (ACE) activity is highly heritable and has been associated with cardiovascular disease. We are studying the effects of genes and environmental factors on hypertension and related phenotypes, such as ACE activity, in Mexican-American families. In the current study, we performed multipoint linkage analysis to search for quantitative trait loci (QTLs) that affect ACE activities on data from 793 individuals from 29 pedigrees from the San Antonio Family Heart Study. As expected, we obtained strong evidence (maximum log of the odds [LOD]ϭ4.57, genomic Pϭ0.003) that a QTL for ACE activity is located on chromosome 17 near the ACE structural locus. We subsequently performed linkage analyses conditional on the effect of this QTL and obtained strong evidence (LODϭ3.34) for a second QTL on chromosome 4 near D4S1548. We next incorporated the ACEIns/Del genotypes in our analyses and removed the evidence for the chromosome 17 QTL (maximum LODϭ0.60); however, we retained our evidence for the QTL on chromosome 4q. We conclude that the QTL on chromosome 17 is tightly linked to ACE and is in strong disequilibrium with the insertion/deletion polymorphism, which is consistent with other reports. We also have evidence that an additional QTL affects ACE activity. Identification of this additional QTL might lead to alternate means of prophylaxis. Key Words: ethnic groups Ⅲ blood pressure Ⅲ genetics Ⅲ hypertension, genetic S erum angiotensin-converting enzyme (ACE) activities are highly heritable, and polymorphisms in the ACE structural locus has been reported to account for 19% to 50% of the variation in serum ACE activity. 1 A common Alu repeat insertion/deletion (I/D) in ACE has been associated with increased blood pressure or risk of cardiovascular disease (CVD) in some, but not all, studies. 2 Because the I/D polymorphism resides in an intron, these inconsistent associations might imply that the functional polymorphism is located elsewhere within the ACE locus or even in a nearby gene. Alternatively, these observations might be indicative of the presence of additional genes or genotypeϫenvironment interactions.We are studying genes, environmental factors, and their interactions that influence blood pressure regulation as part of the San Antonio Family Heart Study (SAFHS). In this study, we report the results of our multipoint linkage analyses to detect quantitative trait loci (QTLs) that affect ACE activities and the relation between the I/D polymorphism and the QTLs in a group of large Mexican-American families. Methods SubjectsWe collected systolic and diastolic blood pressure and ACE activity data on 935 Mexican-Americans who had participated in the SAFHS, a population-based, prospective family study of atherosclerosis and its risk factors. 3 Probands (aged 40 to 60 years) for each family were identified from a low-income neighborhood by a house-to-house recruitment procedure. All first-, second-, and thirddegree relatives of each proband and the proband's spouse were invited to participate...

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Section: Phenotypes and Genotypesmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Two Quantitative Trait Loci Affect ACE Activities in Mexican-Americans

et al. 2004

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“…Current knowledge about the genetic architecture underlying variation in baboon serum ACE activity suggests gene-specific similarities to humans. In particular, interindividual variation in circulating ACE has been demonstrated to have a heritable component in baboons attributable in part to a locus on baboon chromosome 17 near the baboon homologue of the human ACE gene (Kammerer et al, 2003). This evidence suggests that a segregating variant in the baboon ACE gene may associate with variation in baboon ACE activity in a manner similar to that observed in humans.…”

mentioning

confidence: 89%

“…ACE polymorphism Kammerer et al (2003) identified a major quantitative trait locus (QTL) for variation in baboon ACE protein activity located near the baboon ACE homologue on chromosome 17. This result is consistent with a number of studies that have identified functionally important variation in nonhuman primates at or near sites homologous to known functional variants in humans (Trefilov et al, 2000;Newman et al, 2005;Loisel et al, 2006;Wooding et al, 2006).…”

Section: Identification Of a Baboon-specificmentioning

confidence: 99%

“…Aliquots were used only once each in order to minimize freeze-thaw effects on protein viability. Although spectrophotometric quantification of ACE activity by FAPGG cleavage was developed in humans, previous work has shown that this methodology is also applicable to baboons (Kammerer et al, 2003), most likely because of the high amino acid sequence conservation between the ACE proteins of humans and cercopithecine primates (comparison of the publicly available ACE sequence from the human and macaque genomes shows *97% sequence identity).…”

Section: Ace Serum Assaymentioning

confidence: 99%

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Parallel effects of genetic variation in ACE activity in baboons and humans

Tung

Rudolph

Altmann

et al. 2007

American J Phys Anthropol

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Like humans, savannah baboons (Papio sp.) show heritable interindividual variation in complex physiological phenotypes. One prominent example of such variation involves production of the homeostatic regulator protein angiotensin converting enzyme (ACE), which shows heritable variation in both baboons and humans. In humans, this phenotypic variation is associated with an Alu insertion-deletion polymorphism in the ACE gene, which explains approximately half of the variation in serum ACE activity. We identified a similar Alu insertion-deletion polymorphism in the baboon ACE homologue and measured its frequency in a wild population and a captive population of baboons. We also analyzed the contribution of ACE genotype at this indel to variation in serum ACE activity in the captive population. When conditioned on weight, a known factor affecting ACE activity in humans, age and ACE genotype both accounted for variance in ACE activity; in particular, we identified a significant nonadditive interaction between age and genotype. A model incorporating this interaction effect explained 21.6% of the variation in residual serum ACE activity. Individuals homozygous for the deletion mutation exhibited significantly higher levels of ACE activity than insertion-deletion heterozygotes at younger ages (10-14 years), but showed a trend towards lower levels of ACE activity compared with heterozygotes at older ages (> or =15 years). These results demonstrate an interesting parallel between the genetic architecture underlying ACE variation in humans and baboons, suggesting that further attention should be paid in humans to the relationship between ACE genetic variation and aging.

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Baboon Model for Dyslipidemia and Atherosclerosis

Rainwater

VandeBerg

2009

The Baboon in Biomedical Research

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Two Loci Affect Angiotensin I–Converting Enzyme Activity in Baboons

Cited by 7 publications

References 28 publications

Two Quantitative Trait Loci Affect ACE Activities in Mexican-Americans

Two Quantitative Trait Loci Affect ACE Activities in Mexican-Americans

Parallel effects of genetic variation in ACE activity in baboons and humans

Baboon Model for Dyslipidemia and Atherosclerosis

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