Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Diabetic Albuminuria in Patients with NIDDM Followed Up for 9 Years

Xiao-hong, Huang; Rantalaiho, Vappu; Wirta, Ole; Pasternack, Amos; Hiltunen, Timo P.; Koivula, Timo; Malminiemi, Kimmo; Nikkari, T.; Lehtimäki, Terho

doi:10.1159/000045120

Cited by 23 publications

(14 citation statements)

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“…This is in agreement with earlier reports on ACE polymorphism and blood pressure in patients with IgAN [9, 12, 13]. Nor did we find any association between ACE genotypes and other cardiovascular risk factors which accords with an earlier study on the effect of ACE polymorphism in diabetic nephropathy [24]. …”

Section: Discussionsupporting

confidence: 93%

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Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Syrjänen

Xiao-hong²,

Mustonen³

et al. 2000

Nephron

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Background/Aim: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. Methods: A total of 168 patients with IgAN were followed up for 6–17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 µM (1.4 mg/dl) in men or 105 µM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. Results: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria ≧1 g/24 h at the time of renal biopsy, proteinuria ≧1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. Conclusions: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (≧1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.

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Section: Discussionsupporting

confidence: 93%

“…For instance, angiotensin II has growth-promoting effects in mesangial and tubular cells [23]. The II genotype has also been associated with a stable renal function in patients with non-insulin dependent diabetes mellitus [24]. …”

Section: Discussionmentioning

confidence: 99%

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Syrjänen

Xiao-hong²,

Mustonen³

et al. 2000

Nephron

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“…The eGFR inevitably declines with age [1,36,37,38,39,40,41]. The average rate of decline in eGFR due to age has been studied in many cross-sectional and a few longitudinal studies.…”

Section: Proposed Dynamic Redefinition Of Ckdmentioning

confidence: 99%

Rate of Change in Kidney Function and the Risk of Death: The Case for Incorporating the Rate of Kidney Function Decline into the CKD Staging System

Al‐Aly

Cepeda

2011

Nephron Clin Pract

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Chronic kidney disease (CKD) is associated with increased risk of death. A wave of recent studies used longitudinal data to examine the effect of the rate of decline of kidney function on the risk of death. The results from these studies show that there is an independent and graded association between the rate of kidney function decline and the risk of death. There is a need to incorporate the rate of decline in the definition of CKD. This redefinition of CKD will transform a static definition into a dynamic one that more accurately describes the disease state in an individual patient.

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“…ACE, a key enzyme in the renin-agiotensin system, catalyzes the conversion of angiotensin I to angiotensin II in liver and inactivates bradykinin in many tissues. ACE insertion/deletion (I/D) polymorphism, characterized by the presence (insertion) or absence (deletion) of a 287-bp AluI-repeat sequence inside intron 16, has been suggested to be associated with coronary heart disease and nephropathy in type 2 diabetic patients (3)(4)(5)(6)(7)(8)(9). Association studies of ACE I/D polymorphism and type 2 diabetes in various populations have yielded conflicting results (10 -13).…”

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Insertion/Deletion Polymorphism of the ACE Gene Is Associated With Type 2 Diabetes

Feng

Niu

et al. 2002

Diabetes

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In an attempt to examine the role of an ACE gene insertion/deletion (I/D) polymorphism in type 2 diabetes, we conducted a case-control association study among 132 couple-pairs from northern China. The genotype frequencies for II, ID, and DD were 39.8, 39.8, and 20.3%, respectively, in the case group and 44.8, 44.8, and 10.4% in the control group. The DD frequency was significantly higher in the case group than in the control group ( 2 1 ‫؍‬ 4.77, P ‫؍‬ 0.03), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study population. Diabetes 51: 1986 -1988, 2002 T ype 2 diabetes is a complex disorder accounting for ϳ90 -95% of all diabetes syndromes. Despite numerous reports suggesting a substantial genetic contribution to the susceptibility of type 2 diabetes, no major susceptibility genes have been identified so far (1, 2). ACE, a key enzyme in the renin-agiotensin system, catalyzes the conversion of angiotensin I to angiotensin II in liver and inactivates bradykinin in many tissues. ACE insertion/deletion (I/D) polymorphism, characterized by the presence (insertion) or absence (deletion) of a 287-bp AluI-repeat sequence inside intron 16, has been suggested to be associated with coronary heart disease and nephropathy in type 2 diabetic patients (3-9). Association studies of ACE I/D polymorphism and type 2 diabetes in various populations have yielded conflicting results (10 -13). Here, we report a case-control association study of ACE I/D polymorphism and type 2 diabetes in a Chinese population.We tested the relationship between ACE I/D polymorphism and type 2 diabetes in 132 Chinese spousal casecontrol pairs, each pair consisting of a type 2 diabetes proband and his/her nondiabetic spouse. Every proband met the World Health Organization criteria for type 2 diabetes and had at least one first-degree family relative (parent or sibling) with type 2 diabetes. Each nondiabetic spouse control had to be free from any family history of type 2 diabetes and had to have normal glucose tolerance during a 75-g oral glucose tolerance test (OGTT). The phenotypic characteristics of the diabetic and spousal control subjects are summarized in Table 1. Age and sex were well matched between the case and the control groups, whereas the average BMI, waist-to-hip ratio, blood pressure, and serum concentrations of insulin, C-peptide, total cholesterol, and triglycerides were significantly higher in the case subjects. The genotype frequencies of ACE gene I/D polymorphism were shown in Table 2.The D allele frequency was 40.2 and 32.8% in the case and the control groups, respectively, which is in line with previous reports of 29.3-41.6% frequencies in other Asian populations (5,10,11,13) and is much lower than the 52-57% frequencies reported in Caucasian populations (12,14,15). The observed genotype distribution was in Hardy-Weinberg equilibrium in control subjects ( 2 1 ϭ 0.03, P ϭ 0.96) and was marginally deviated from the equilibrium in case subjects ( 2 1 ϭ 3.77, P ϭ 0.05). A signif...

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Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Diabetic Albuminuria in Patients with NIDDM Followed Up for 9 Years

Cited by 23 publications

References 34 publications

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Rate of Change in Kidney Function and the Risk of Death: The Case for Incorporating the Rate of Kidney Function Decline into the CKD Staging System

Insertion/Deletion Polymorphism of the ACE Gene Is Associated With Type 2 Diabetes

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