Angiotensin I–converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an Italian population

Stratta, Piero; Canavese, Caterina; Ciccone, Giovannino; Barolo, Stefano; Dall’Omo, Anna Maria; Fasano, Maria Edvige; Mazzola, Gina; Berutti, Silvia; Fop, Fabrizio; Curtoni, E. S.; Piccoli, Giuseppe

doi:10.1016/s0272-6386(99)70144-7

Cited by 29 publications

(32 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, although some reports indicate a possible relationship between ACE gene I/D polymorphism and the progression of IgAN [11,12,13,14,15], others have failed to obtain similar results [16,17,18,19,20,21]. On the issues of IgAN susceptibility, the results are also inconsistent [11,12,13,14,15,16,17,18,19,20,21]. The contradictory findings could be explained by many factors, including variable sample size, racial differences, population stratification, phenotype difference, as well as the extent and degree of linkage disequilibrium between the marker tested and the causal variants, etc.…”

Section: Introductionmentioning

confidence: 99%

Association of Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and IgA Nephropathy: A Meta-Analysis

Du¹,

Qing²,

Liu³

et al. 2006

Am J Nephrol

View full text Add to dashboard Cite

Background/Aims: The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been extensively examined for the association with immunoglobulin A (IgA) nephropathy (IgAN), however, conflicting results have occurred. We performed a meta-analysis to evaluate the association of ACE I/D polymorphism with IgAN in different ethnic groups. Methods: 11 studies testing the association between ACE I/D polymorphism and IgAN susceptibility, and 9 studies testing the association of ACE I/D with IgAN progression were used in this analysis. The overall odds ratio (OR) was estimated by a fixed or random effect model. Results: The overall OR for the risk of susceptibility and progression of IgAN in Asians for the DD genotype is 2.37 (95% CI 1.04–5.41) and 1.75 (95% CI 1.24–2.56). The overall OR for the D allele in Asians also showed a similar magnitude, though without statistical significance (p = 0.09, p = 0.13, respectively). In Caucasians, both the DD genotype and D allele were associated with IgAN progression (OR 1.90, 1.61, respectively), but not IgAN susceptibility (p = 0.30, p = 0.41, respectively). Conclusion: Our findings support the notion that ACE I/D polymorphism is associated with IgAN. Meanwhile, the role of ACE I/D polymorphism in Asians is different from that of Caucasians.

show abstract

Section: Introductionmentioning

confidence: 99%

Association of Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and IgA Nephropathy: A Meta-Analysis

Du¹,

Qing²,

Liu³

et al. 2006

Am J Nephrol

View full text Add to dashboard Cite

show abstract

“…In other diseases that affect the kidney, such as diabetes or IgA nephropathy, subjects carrying the D allele also have the highest risk of the development of renal failure. 9,10 Furthermore, the D allele has been linked to a failure of the renoprotective action of ACE inhibitors (ACEIs) to retard the development of end-stage renal disease. 11,12 The influence of the I/D polymorphism on the outcome of microalbuminuria has not been explored in essential hypertension, and the objective of the present study was to analyze this relationship in patients receiving antihypertensive treatment during a 3-year follow-up period.…”

mentioning

confidence: 99%

Influence of the I/D Polymorphism of the Angiotensin-Converting Enzyme Gene on the Outcome of Microalbuminuria in Essential Hypertension

et al. 2000

View full text Add to dashboard Cite

Abstract-The objective of the present study was to analyze the influence of the I/D polymorphism of the ACE gene on the outcome of microalbuminuria in essential hypertensive patients who were receiving antihypertensive treatment. One hundred thirty-six essential hypertensive patients who were Ͻ50 years old and had never previously received treatment with antihypertensive drugs were included in the study. During a 3-year period, patients received nonpharmacological treatment consisting of moderate salt restriction and a low-calorie diet they were obese, with or without a regimen of antihypertensive drugs based on ␤-blockers or ACE inhibitors. Hydrochlorothiazide was added when necessary to maintain the blood pressure goal of Ͻ135/85 mm Hg. At the beginning of the study and at yearly intervals, systolic and diastolic blood pressures (SBP and DBP, respectively), 24-hour urinary albumin excretion (UAE), renal function, and biochemical profile measurements were made. The insertion/deletion (I/D) polymorphism of the ACE gene was determined through the use of polymerase chain reaction. The variables used in the statistical analysis were the measurements at the start of the study and the increase or decrease detected during the follow-up, estimated as individual specific regression line slope values. At baseline, no differences in blood pressure or UAE values were observed among genotypes. Likewise, the genotype or allele frequency was not significantly different between normoalbuminurics and microalbuminurics. After the 3 treatment years, significant reductions in SBP, DBP, and UAE were found (SBP 151.6Ϯ17.3 reduced to 137.2Ϯ14.3 mm Hg, PϽ0.001; DBP 96.6Ϯ8.9 reduced to 84.5Ϯ9.8 mm Hg, PϽ0.001; UAE 36.7Ϯ71.5 reduced to 28.3Ϯ78.6 mg/24 h, PϽ0.05). The slopes of these parameters over time did not differ significantly among genotypes. The slope of SBP was the main factor related to the slope of logUAE (PϽ0.003). A significant positive correlation coefficient between the SBP and logUAE slopes was observed for the DD patients (rϭ0.57, PϽ0.0001) but was absent in patients carrying the I allele (II rϭϪ0.03, PϭNS; I/D rϭ0.01, PϭNS). Follow-up studies should be used to achieve a better understanding of the impact of candidate gene polymorphisms on the development of hypertension-induced organ damage. Assessment of the I/D polymorphism of the ACE gene may identify subjects who require a greatly lowered blood pressure to prevent organ damage and to reduce hypertensionassociated complications and death.

show abstract

“…Yorioka et al [30]showed that either the ID or the DD genotype was associated with a more rapid rate of decline in GFR. Others have confirmed these findings [31, 32]and associated the D allele with earlier onset, proteinuria, hypertension, and the risk of ESRD.…”

Section: Renin-angiotensin Systemmentioning

confidence: 63%

Molecular Genetics in IgA Nephropathy

Galla¹

2001

Nephron

View full text Add to dashboard Cite

Evidence from both genotypic and phenotypic perspectives is considered that patients may be genetically predisposed to IgA nephropathy (IgAN) or Henoch-Schönlein purpura (HSP) or that a factor(s) might exclusively contribute to their progression to chronic renal failure. In contrast to most other renal diseases, both IgAN and HSP are uncommon in blacks; this is unexplained but is not due to their low frequency of the A2m(1) allotype. The association of these diseases or their progression with a variety of abnormalities of IgA immunobiology in patients and their families has not been linked to any genotype; similarly, no HLA antigen has been positively or negatively associated in any consistent way. Although complement factor 3 universally accompanies IgA glomerular deposition, complement pathway abnormalities are only sporadically reported with either IgA deposition or disease progression. Whether angiotensin-related polymorphism including the converting enzyme alleles have a specific predictable role, particularly in the progression of renal failure in IgAN, remains problematic. The promising possibility that a structural defect in IgA1 due to an as yet unidentified genetic defect accounts for the deposition of IgA is considered in some detail. Nevertheless, the genetic mechanism(s) of progressive renal failure, whether exclusive to IgAN or to glomerular diseases generally, is of paramount importance.

show abstract

Angiotensin I–converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an Italian population

Cited by 29 publications

References 49 publications

Association of Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and IgA Nephropathy: A Meta-Analysis

Association of Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and IgA Nephropathy: A Meta-Analysis

Influence of the I/D Polymorphism of the Angiotensin-Converting Enzyme Gene on the Outcome of Microalbuminuria in Essential Hypertension

Molecular Genetics in IgA Nephropathy

Contact Info

Product

Resources

About