P3571Genes polymorphism and renal dysfunction formation in arterial hypertension patients with high adherence to treatment

Abstract

Abstract Objective To evaluate the contribution of gene polymorphism to the formation of renal dysfunction in patients with hypertension with high adherence to treatment. Methods and materials 88 working-aged subjects with non-complicated arterial hypertension (average age 48,65±7,24 yrs). All patients underwent evaluation of genotype for markers AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met. To assess the glomerular function, cystatin C was measured in serum by ELISA, and serum level of NGAL was determined by ELISA to assess the function of the tubules.Depending on genotype peculiarities the following groups were formed: 1) 39 patients who had polymorphism of AGT Thr174Met in homozygous and 49 subjects without one; 2) 62 subjects who had polymorphism of GNB3 C825T in heterozygous and 26 subjects without one; 3) 52 subjects with polymorphism of MTHFR C677T in heterozygous and 36 subjects without one; 4) 48 subjects with polymorphism of MTRR Ile22Met in heterozygous and 40 subjects without one. Results Patients in the groups did not differ in sex, age, risk factors, comorbidities, concomitant medications, BP level, lipid spectrum. In the groups with the presence of the genes GNB3 and MTHFR polymorphism in the heterozygous form, the level of NGAL was significantly higher than in the groups with normal genotypes: 1.67±0.86 ng/ml versus 1.2±0.87 pg/ml (p=0.022), 1.49±0.61 pg/ml versus 1.21±0.56 ng/ml (p=0.034), respectively. At the same time, in these groups, the level of cystatin C was not significantly different. The AGT gene polymorphism groups differed significantly in cystatin C (p<0.001), but did not differ in the level of NGAL. In the group with the presence of the MTRR gene polymorphism, the level of cystatin C and the level of NGAL were significantly higher (p=0.042 and p=0.004, respectively). The correlation analysis revealed a moderate direct interconnections between cystatin C levels and the presence of the AGT gene polymorphism (r=0.46; p=0.017) and MTRR (r=0.33; p=0.039), as well as between the NGAL level and the presence of the GNB3 gene polymorphism (r=0.42; p=0.031), MTHFR (r=0.39; p=0.023) and MTRR (r=0.43; p=0.007). Conclusions In working-aged patients with uncomplicated hypertension with high adherence to treatment, the formation of renal dysfunction with a primary glomerular lesion is associated with the presence of polymorphism of the AGT gene in the heterozygous form. Formation of renal dysfunction with predominant tubular lesion is associated with the presence of GBN3 and MTHFR genes polymorphism of in the heterozygous form. And the formation of renal dysfunction with the damage of both glomeruli and tubules is associated with the presence of the MTRR gene polymorphism of the in the heterozygous form.