Preventing end stage renal disease in diabetic patients — genetic aspect (part I)

Jacobsen, Peter Karl

doi:10.3317/jraas.2005.001

Cited by 31 publications

(38 citation statements)

References 177 publications

(257 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Baseline characteristics of the patients according to the ACE insertion/deletion genotypes were similar, except for race and 2 , P Ͻ 0.05). The difference in BMI between genotypes was not significant after adjustment for race (P ϭ 0.557), whereas the trend to a difference in glycosylated hemoglobin became significant after adjustment for race (P ϭ 0.020).…”

Section: Resultsmentioning

confidence: 78%

ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy

Parving¹,

Zeeuw²,

Cooper³

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Losartan treatment reduced renal outcomes in proteinuric patients with type 2 diabetes in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. It is unknown whether an insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene predicts renal outcomes and death and influences the effect of losartan in these patients. Pharmacogenetic analyses were performed comparing losartan with placebo administered with conventional blood pressure-lowering therapy in 1435 (95%) of the 1513 RENAAL study patients. The primary endpoint was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease (ESRD) or death. Cox regression models were stratified on baseline proteinuria and included treatment, geographic region, ACE/ID genotype, and treatment ϫ genotype interaction. Within the placebo group, subjects with the ID or DD genotype were more likely than those with the II genotype to reach the composite endpoint (by 17.5% and 38.1%, respectively, P ϭ 0.029) or its individual components. Within the losartan group, genotype did not correlate with reaching the composite endpoint. Compared with placebo, however, losartan reduced the risk of reaching the composite endpoint by 5. 8% (95% confidence interval, Ϫ23.3, 28.0), 17.6% (3.8, 29.4), and 27.9% (7.0, 44.1) among those with the II, ID, and DD genotypes, respectively. Similar trends were demonstrated for the individual endpoints. In conclusion, proteinuric type 2 diabetic patients with the D allele of the ACE gene have an unfavorable renal prognosis, which can be mitigated and even improved by losartan.

show abstract

Section: Resultsmentioning

confidence: 78%

ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy

Parving¹,

Zeeuw²,

Cooper³

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Sums with increasing numbers of SNP markers (i.e. n) were formed, starting with the markers ranked highest S (n=1) = s (1) ; S (n=2) =s (1) +s (2) , and so on. The primary interest was to find the n of SNPs in S that reflects the association of this set of markers with the disease.…”

Section: Description Of Gene Variants and Genotyping Methodsmentioning

confidence: 99%

“…It has been established that the onset and progression of DN are genetically determined [2,3]. Ethnic differences in prevalence, uneven incidence over the time-course of the disease (culminating in the second decade of diabetes duration) [4], familial clustering in different populations for both type 1 and 2 diabetes [5][6][7][8][9][10][11][12][13], and the results of segregation analyses [14,15] suggest the existence of susceptibility genes for DN in addition to those leading to diabetes.…”

Section: Introductionmentioning

confidence: 99%

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single-and multi-locus analyses. Materials and methods The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCRbased methodology (PCR only, PCR plus RFLP, or allelespecific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis.

show abstract

“…It has been suggested that ACE inhibitor therapy might be more benefit in the early stages of diabetic nephropathy, whereas in more advanced stages treatment appears to confer consistent renoprotection to all patients regardless of their ACE I/D genotypes (5). Among patients with overt nephropathy (43) an association between the I allele with a slower progression to doubling of serum creatinine or ESRD was observed. Also, it has been demonstrated that GFR decline over time was significantly slower in patients carrying one or two copies of I allele compared to D allele (44).…”

Section: Ace I/d Polymorphism and Response To Therapymentioning

confidence: 98%

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Rahimi¹

2012

J Nephropathol

View full text Add to dashboard Cite

Implication for health policy/practice/research/medical education:The presence of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with highest systemic and renal ACE levels, compared with the lowest ACE activity in carriers of II genotype. Most studies confirmed that ACE I/D polymorphism is involved in the susceptibility to overt nephropathy with protective role of ACE II genotype against the disease in both type 1 and 2 diabetes mellitus. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Results:The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. Conclusions: In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.Review Article

show abstract

Preventing end stage renal disease in diabetic patients — genetic aspect (part I)

Cited by 31 publications

References 177 publications

ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy

ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Contact Info

Product

Resources

About