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An Insertion/Deletion Polymorphism in Angiotensin- Converting Enzyme (ACE) and Diabetic Nephropathy

Diabetic nephropathy is a chronic, microvascular complication of diabetes. It is still a puzzle why some diabetics never develop nephropathy and others with mild signs of diabetes rapidly develop this disease. A hypothesis assumes, among other factors, a genetic susceptibility for developing diabetic nephropathy and involves the angiotensin- converting enzyme (ACE) insertion/deletion (ACE I/D) polymorphism, with the D allele being the risk factor. ACE exerts its effects mainly by catalyzing the conversion of inactive angiotensin I to active angiotensin II, but also by inactivating the vasodilatory peptide bradykinin. The aim of this study was to investigate the allelic distribution of the ACE I/D polymorphism in diabetics without signs of renal failure and those in the end-stage of renal failure. Blood samples were taken from 201 patients with diabetes type 2 divided into 2 groups: 1) those with nephropathy receiving some form of renal replacement therapy, and 2) long-standing diabetics without signs of nephropathy. DNA was isolated from venous EDFTA-blood with G-spinTM Genomic DNA Extraction Kit (iNtRON Biotechnology). Genotyping was carried out using primers and fluorescent labeled probes in a LightCycler System (Roche Diagnostics). The ACE gene, common insertion/deletion (I/D) polymorphism is defined by the presence or absence of a 287 bp fragment inside intron 16. Departures from Hardy-Weinberg equilibrium, genotype- and allele-specific case- control associations were assessed using a χ2 test. Genotype frequencies of the ACE I/D polymorphism were in accordance with the Hardy- Weinberg equilibrium (df=1). Global genotype- specific test in co-dominant model: χ2 =4.461, df=2, P=0.107. There is no significant differences between recesive and dominant models: OR (II vs DD) = 0.44 (0.31-0.95) P=0.035 ; OR (ID vs DD) = 0.68 (0.36-1.29) P=0.257. Test of allele specific case control associations showed frequencies for (I, control)=0.51 ; freq (I, case) = 0.40 OR (I vs D) = 0.64 (0.43-0.95), P=0.027. Our results referee that further studies based on a larger number of samples and/or comprising more SNPs are warranted to confirm or reject the reported phenotype–genotype associations

diabetic nephropathy ; angiotensin-converting enzyme (ACE) ; insertion/deletion polymorphism

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