Key result
Angiotensinogen gene TT allele linked to ~28-fold higher odds of diabetic nephropathy versus MM genotype.
Observational (n=79)
Odds Ratio: 28.389
p-value: p=< 0.01
The TT genotype of the angiotensinogen gene M235T polymorphism is strongly associated with the presence of proteinuria in patients with type 1 diabetes mellitus.
Hypertension and TT AGT M235T genotype were associated with proteinuria in T1DM; leaves open whether genotyping improves risk stratification.
BACKGROUND/AIM: Diabetic nephropathy (DN) as a major microvascular complication of diabetes mellitus (DM) include a progressive increase in urinary albumin excretion in association with an increase in blood pressure and to end stage renal failure. Hypertension connected with renin-angiotensin system (RAS) hyperactivity and corresponding genotypes, angiotensinogen (AGT), angiotensine-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R), predispose the increasing risk of DN. The aim of this study was to assess the distribution of AGT, ACE and AT1R gene polymorphisms in patients with type 1 DM according to the level of DN and patients clinical characteristics. METHODS: The study included 79 type 1 diabetic patients. Inclusion criteria were: age between 20-40, duration of diabetes > 5 years, and no other severe diseases. Clinical characteristics were gained from interviewing the patients. Polymorphism was detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism using restriction enzymes Psy I (Tth 111 I) and Hae III. RESULTS: The patients with proteinuria compared with normo- and microalbuminuric patients, highly differed in age, diabetes duration, blood pressure level, hypertension, rethynopathy and urinary albumin excretion values (p < 0.001). No statistically significant difference between the groups was found for the ACE and AT1R gene polymorphisms distribution. The presence of TT genotype of the M235T polymorphism was significantly higher in the group with proteinuria (p < 0.05). The patients with hypertension raised nephropathy 5.2 times higher (OR = 5.20, p < 0.05) while carriers of TT allel developed nephropathy 28.38 times higher (OR = 28.389, p < 0.01) than those with MM genotype. CONCLUSION: Increased association of hypertension and TT angiotensinogen gene polymorphism in patients with diabetes mellitus with proteinuria could be a significant marker of diabetic nephropathy.
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Ilić et al. (2014) conducted an observational in Type 1 diabetes mellitus (n=79). TT angiotensinogen gene polymorphism vs. MM genotype was evaluated on Diabetic nephropathy (OR 28.389, p=< 0.01). Carriers of the TT allele of the angiotensinogen gene had significantly higher odds of developing diabetic nephropathy compared to those with the MM genotype (OR 28.389, p<0.01).
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