Two Quantitative Trait Loci Affect ACE Activities in Mexican-Americans

Kammerer, Candace M.; Gouin, Nicolás; Samollow, Paul B.; VandeBerg, Jane F.; Hixson, James E.; Cole, Shelley A.; MacCluer, Jean W.; Atwood, Larry D.

doi:10.1161/01.hyp.0000111830.36999.94

Cited by 31 publications

(30 citation statements)

References 22 publications

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“…41 The possibility of another functional polymorphism in the 5Ј region cannot be excluded, 35,44 and the presence of yet another QTL, located on chromosome 4, was recently suggested. 45 An immense number of studies were published investigating associations of the I/D polymorphism with different pathophysiological conditions. Many studies found significant associations, whereas others did not confirm those findings.…”

Section: Discussionmentioning

confidence: 99%

“…35 The presence of yet another QTL, located on chromosome 4, was recently suggested. 45 In a multipoint linkage analysis performed in 29 pedigrees from the San Antonio Family Heart Study, Kammerer et al 45 showed strong evidence that a QTL located on chromosome 17 near the ACE structural locus, and a second QTL on chromosome 4 near marker D4S1548, were both associated with plasma ACE levels. The evidence for the presence of this new QTL remained strong, even after adjustment for the first QTL near the ACE gene.…”

Section: Functional Polymorphisms In the Ace Genementioning

confidence: 99%

“…The evidence for the presence of this new QTL remained strong, even after adjustment for the first QTL near the ACE gene. 45 The nature of this new locus remains unknown. If the new QTL represents a regulatory gene, this discovery might help explain some of the paradoxical results regarding the relation between the ACE gene, ACE activity, and clinical outcomes, and might help in the development of alternative means of prophylaxis and treatment.…”

Section: Functional Polymorphisms In the Ace Genementioning

confidence: 99%

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ACE Polymorphisms

Sayed‐Tabatabaei

Oostra

Isaacs

et al. 2006

Circulation Research

382

334

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Abstract-Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3Ј UTR. The potential existence of another functional polymorphism in the 5Ј UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.

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Section: Discussionmentioning

confidence: 99%

Section: Functional Polymorphisms In the Ace Genementioning

confidence: 99%

Section: Functional Polymorphisms In the Ace Genementioning

confidence: 99%

See 1 more Smart Citation

ACE Polymorphisms

Sayed‐Tabatabaei

Oostra

Isaacs

et al. 2006

Circulation Research

382

334

View full text Add to dashboard Cite

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“…Whether this is also the case among Colombians is currently unknown. However, Kammerer et al (25) have shown that the levels of ACE activity increase progressively with the number of D alleles in Mexican-Americans, a population that shares some ancestry with Colombians.…”

Section: Discussionmentioning

confidence: 99%

Population-Based Case-Control Study of Renin-Angiotensin System Genes Polymorphisms and Hypertension among Hispanics

Bautista¹,

Vargas

Oróstegui

et al. 2008

Hypertens Res

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The effect of polymorphisms of the RAS genes on the incidence of hypertension seems to be populationdependent. We studied the effects of the angiotensinogen T174M and M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of hypertension among Hispanics. We selected all cases (n =256) and 257 age and sex groupmatched controls from a random sample of free living Colombians (n =2,989). Logistic regression was used to estimate the independent effect of each polymorphism. All polymorphisms were in Hardy-Weinberg equi-

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“…Furthermore, an interaction between the ACE I/D polymorphism and a QTL on chromosome 4 has been discussed as cause for the variances in ACE levels (Kammerer et al 2004). Despite the comparable shortness of the ACE gene (21 kb only), these conflicting results indicate how strenuous the unravelling of complex genetic mechanisms can be (Fig.…”

Section: Polymorphisms In the Angiotensin Converting Enzymementioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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Two Quantitative Trait Loci Affect ACE Activities in Mexican-Americans

Cited by 31 publications

References 22 publications

ACE Polymorphisms

ACE Polymorphisms

Population-Based Case-Control Study of Renin-Angiotensin System Genes Polymorphisms and Hypertension among Hispanics

Genetics of arterial hypertension and hypotension

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