Genetic polymorphisms of the renin–angiotensin system and complications of insulin‐dependent diabetes mellitus

Ittersum, Frans J. van; Man, A. M. E. de; Thijssen, Sandra; Knijff, Peter de; Slagboom, P. Eline; Smulders, Yvo M.; Tarnow, Lise; Donker, A. J. M.; Bilo, Henk J. G.; Stehouwer, Coen D.A.

doi:10.1093/ndt/15.7.1000

Cited by 66 publications

(36 citation statements)

References 30 publications

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“…Apparently contrary to the present observations, no associations of AGT 235M/T polymorphism or interactions between AGT 235M/T, I/D ACE, or/and 1166A/C polymorphisms with regard to cardiovascular disease were found by van Ittersum et al (39) in the cross-sectional Dutch study comprising 257 subjects with type 1 diabetes. Surprisingly, in this study, the use of ACEIs was not included as a covariate in logistic regression analysis of CAD risk (39). Because in our study, the effect of RAS gene variants is highly related to ACEI/ARB treatment, we cannot be sure that the results of two studies are different.…”

Section: Discussioncontrasting

confidence: 99%

“…The role of genetic factors associated with premature coronary atherosclerosis in subjects with type 1 diabetes has not been intensively studied yet. To our knowledge, there is only one published study that analyzed the same genetic variants of RAS as evaluated in the present study (39). Apparently contrary to the present observations, no associations of AGT 235M/T polymorphism or interactions between AGT 235M/T, I/D ACE, or/and 1166A/C polymorphisms with regard to cardiovascular disease were found by van Ittersum et al (39) in the cross-sectional Dutch study comprising 257 subjects with type 1 diabetes.…”

Section: Discussioncontrasting

confidence: 85%

“…To our knowledge, there is only one published study that analyzed the same genetic variants of RAS as evaluated in the present study (39). Apparently contrary to the present observations, no associations of AGT 235M/T polymorphism or interactions between AGT 235M/T, I/D ACE, or/and 1166A/C polymorphisms with regard to cardiovascular disease were found by van Ittersum et al (39) in the cross-sectional Dutch study comprising 257 subjects with type 1 diabetes. Surprisingly, in this study, the use of ACEIs was not included as a covariate in logistic regression analysis of CAD risk (39).…”

Section: Discussioncontrasting

confidence: 85%

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Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis

Krętowski

McFann

Hokanson³

et al. 2007

Diabetes

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Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6 -388], P ‫؍‬ 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes. Diabetes 56:863-871, 2007 P atients with type 1 diabetes have a dramatically higher risk of coronary artery disease (CAD) compared with the general population (1,2). Coronary artery calcification (CAC), a marker of coronary artery plaque burden, correlates very well with the established CAD risk factor profile in patients with type 1 diabetes (3-5). There is growing evidence that CAC strongly predicts future coronary events in asymptomatic nondiabetic and diabetic subjects (4 -6).Diabetic nephropathy plays an important role in the pathogenesis of advanced CAD in type 1 diabetes (2). However, little is known concerning determinants of subclinical atherosclerosis detected as rapidly progressing CAC. Activation of the renin-angiotensin system (RAS) by hyperglycemia may be the key mechanism (7,8). The RAS involves enzymatic processing of angiotensinogen (AGT) to angiotensin I, further cleaved by ACE to angiotensin II. Treatment with ACE inhibitors lowers the risk of cardiovascular death, myocardial infarction, and coronary revascularization in the general population and in diabetic patients (9 -11).The RAS activity is modified by variants of the genes coding functional proteins of this pathway (12-14). The AGT gene, localized on chromosome 1q41-qter, encodes AGT. There is only one haplotype block at the AGT locus, and all common single nucleotide polymorphisms (SNPs) identified appear to be in complete linkage disequilibrium with the most intensively studied M235T polymorphism (13,15). Although the functional variant has not yet been definitively identified (16), the T235 allele has been consistently associated with cardiovascular disease (13,17) and ...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 85%

Section: Discussioncontrasting

confidence: 85%

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Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis

Krętowski

McFann

Hokanson³

et al. 2007

Diabetes

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show abstract

“…However, the important ones include existence of identifiable human disease from overexpression/mutations/polymorphisms in the renin, angiotensinogen, ACE, AT 1 R, aldosterone, and MR genes (Table 3). This is exemplified in a Dutch cohort with insulin-dependent diabetes mellitus (IDDM)-induced incipient diabetic kidney disease (336). Within this population, the T-allele of the AGT-M235T polymorphism is associated with increases in proteinuria, and the CC-genotype of the AT 1 -A1166C polymorphism is asso-ciated with hypertension.…”

Section: B Raas In the Kidneymentioning

confidence: 99%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

139

123

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“…There were no reports indicated a significant relationship between AGT rs699 and DR, but in patients with incipient diabetic renal failure the T allele of AGT rs699 was associated with DR. In these patients interaction between the D allele of ACE I/D and the T allele of AGT rs699 tended towards protection against DN (Van Ittersum et al, 2000). Oppose, other study indicated that the same interaction increases risk for DN in patients cu DR (Marre et al, 1997).…”

Section: Other Ras Genesmentioning

confidence: 83%