The importance of angiotensin II type 1 receptor gene polymorphism to losartan treatment in improving glomerulopathy in type 1 diabetic patients.

Objective: Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. Aim of this study was to examine if renoprotective response to losartan therapy, in patients with diabetic nephropathy, depends on 1166 A/C gene polymorphism for its target receptor, angiotensin II type 1 receptor (AT1R).

Subjects And Methods: The study included 35 patients with diabetes mellitus type 1 and high urinary albumin excretion rate (>30mg/24h) genotyped for the 1166 A/C gene polymorphism for the AT1R. The participants were segregated into three genotype groups according to combinations of A or C allele: AA-16, AC-15 and CC-4 patients. The patients received losartan 50mg daily for 4 weeks, following 100mg daily for 8 weeks. At baseline and after losartan therapy period, blood pressure, GFR (Gates method) and filtration fraction (FF) were calculated. FF was calculated by dividing GFR by ERPF (Schlegels method).

Results: GFR remained unchanged in all genotype groups. FF was significantly reduced from baseline by 0.018±0.024 (P=0.012) only in the AC group. In the AA genotype FF was reduced from baseline by 0.017±0.03 (P=0.052) and in the CC group by 0.01±0.008 (P=0.092). In the AA group, systolic blood pressure declined from 136±24mmHg at baseline, to an average of 121±18mmHg at the end of the study (P=0.001). The AC group achieved reduction from 131±10mmHg at baseline to 115±7mmHg (P=0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86±13mmHg at baseline to 78±8mmHg (P=0.004), and in the AC genotype from 88±5mmHg at baseline to 11.7±5.6mmHg during the investigation period (P=0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (P=0.066).

Conclusion: The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.