Abstract
Gene polymorphisms associated with the renin-angiotensin-aldosterone system (RAAS) have been extensively studied in diabetic nephropathy (DN) patients, due to therapeutic potential of targeting the RAAS and slowing down the disease progression. The aim of our study was to examine the association between angiotensinogen (AGT) gene polymorphisms (rs699 and rs4762) and DN in Caucasians with type 2 diabetes mellitus (T2DM). A total of 651 unrelated Slovenian (Caucasian) T2DM patients were tested for AGT rs699 and rs4762 polymorphisms using a novel fluorescence-based kompetitive allele-specific polymerase chain reaction (KASPar) assay. A study group consisted of 276 T2DM patients with DN, while control group included 375 patients without DN but who have had T2DM for >10 years. For rs699 polymorphism, the frequencies of GG, GA and AA genotypes were 20.6%, 52.2% and 27.2%, respectively in T2DM patients and 23.4%, 48.1% and 28.5%, respectively in controls. The distributions of GG, GA and AA genotypes for rs4762 polymorphism were 73.9%, 23.2% and 2.9%, respectively in T2DM patients and 70.4%, 27.5% and 2.1%, respectively in controls. No significant differences in the allele frequencies were found between T2DM patients and controls for both polymorphisms. AGT rs699 and rs4762 missense polymorphisms are not associated with DN in our subset of Slovenian T2DM patients.
Highlights
Diabetic nephropathy (DN) is a chronic, progressive microvascular complication of diabetes mellitus
Submitted: 04 December 2016/Accepted: 22 February 2017 progression is therapeutic targeting of the renin–angiotensin–aldosterone system (RAAS) [2,3,4,7,8].This is related to the pathophysiological relationship between DN and increased blood pressure, i.e. type 2 diabetes mellitus (T2DM) and DN are usually associated with hypertension [2,3,7]
All components of the systemic RAAS are present in local RAAS, and for example in the kidneys, the local effects accelerate the progression of renal disease [7,9]
Summary
Diabetic nephropathy (DN) is a chronic, progressive microvascular complication of diabetes mellitus. It is associated with high cardiovascular morbidity and mortality and is still the most common cause of end-stage renal disease (ESRD) in developed countries [1,2,3,4]. Submitted: 04 December 2016/Accepted: 22 February 2017 progression is therapeutic targeting of the renin–angiotensin–aldosterone system (RAAS) [2,3,4,7,8].This is related to the pathophysiological relationship between DN and increased blood pressure, i.e. type 2 diabetes mellitus (T2DM) and DN are usually associated with hypertension [2,3,7]. Urinary AGT was proposed as a possible early marker of DN, as it reflects intrarenal RAAS status in chronic glomerulonephritis [11]
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