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Progression of metabolic disorders, arterial hypertension and chronic kidney disease in patients with excessive body weight: the contribution of polymorphism of the genes of angiotensin, NO-synthase, interleukins-1β and -6

Keywords:

V.I. Sholomova – Respiratory Therapist, Assistant Professor, Lomonosov Moscow State University, Faculty of Base Medicine, Department of Internal Medicine; I.M. Sechenov First Moscow State Medical University, Faculty of Preventive Medicine, Department of Internal, Occupational Diseases and Pulmonology; 3rd Uni-versity Clinic, Department of Pulmonology and Occupational Diseases
E-mail: vsholomova@mail.ru
L.M. Samokhodskaya – Ph.D. (Med.); Associate Professor; Head of Department; Lomonosov Moscow State University, Medical Research and Educational Center (Lomonosov University Clinic)
А.V. Balatskij – Ph.D. (Med.); Senior Research Scientst, Lomonosov Moscow State University, Medical Re-search and Educational Center (Lomonosov University Clinic); Department of Laboratory Diagnostics
M.Yu. Brovko – Ph.D. (Med.), Head of Department; I.M. Sechenov First Moscow State Medical University, 3rd University Clinic, Department of Pulmonology and Occupational Diseases
T.N. Krasnova – Ph.D. (Med.); Associate Professor; Lomonosov Moscow State University, Faculty of Base Medicine, Department of Internal Medicine; I.M. Sechenov First Moscow State Medical University, Faculty of Preventive Medicine, Department of Internal, Occupational Diseases and Pulmonology
E.А.Saginova – Ph.D. (Med.); Assistant Professor, Lomonosov Moscow State University, Faculty of Base Medicine, Department of Internal Medicine
M.Yu. Shvetsov – Ph.D. (Med.); Associate Professor; Lomonosov Moscow State University, Faculty of Base Medicine, Department of Internal Medicine; I.M. Sechenov First Moscow State Medical University, Faculty of Preventive Medicine, Department of Internal, Occupational Diseases and Pulmonology
N.А. Mukhin – Academician of the RAS, Dr.Sc. (Med.), Professor, Head of Department of Internal Medicine; Lomonosov Moscow State University, Faculty of Base Medicine, I.M. Sechenov First Moscow State Medical University, Faculty of Preventive Medicine, Head of Department of Internal, Occupational Diseases and Pulmonology


Among the mechanisms of development and progression of CKD, especially in patients with metabolic disorders and arterial hypertension, particular attention is given to endothelial dysfunction. The endothelium function is affected by NO-synthase, components of the reninangiotensinzinaldosterone system (RAAS) and inflammatory cytokine: TNF, interleukin-1 and interleukin-6, which are also produced in obesity. We studied the influence of angiotensin AGT 704T/C, NO-synthase NOS3 894G/T, interleukin-1β IL1β -511G/A, interleukin-6 IL6 -174G/C gene polymorphism on the formation of CKD in 111 patients with excessive body weight.
In 83 patients (74.8%) carriage of C-allele AGT 704C/C gene was detected: СС in 24 (21.6%) and TC in 59 (53.2%). The se-verity of arterial hypertension was significantly higher in TC genotype than in the TT genotype (p = 0.045). A distinct tendency to increase the severity of AH was observed in the CC genotype (p = 0.085). The CC genotype was characterized by a significantly lower serum cholesterol level compared with the TT genotype (p = 0.030) and a trend toward a difference in comparison with the homo- and heterozygous carriers of the T allele (p = 0.052). The same trend was observed for differ-ences in serum triglyceride levels (p = 0.078).
The G-alleles of the NOS3 894G/T gene were detected in 97 patients (92.4%): GT in 45 (42.9%), GG in 8 (7.6%), and were associated with significantly higher blood pressure (p = 0.021), obesity (p = 0.014), and higher level of glycemia (p = 0.14). There was also a trend toward a higher incidence of diabetes mellitus type 2 in the GG genotype compared to GT and TT genotypes (p = 0.072). A significantly higher level of C-reactive protein was revealed in the TT genotype compared to the GG genotype (p = 0.002).
The G-alleles of the IL1β -511G/A gene were detected in 80 patients (88.9%): GG in 39 (43.3%), GA in 41 (45.6%). Signifi-cantly lower GFR values were observed in the GG- and AA-genotypes in comparison with the GA-genotype (p = 0.016). There was no significant difference in the calculated GFR between GG and AA genotypes. The level of C-reactive protein was significantly lower in the AA genotype than in the GA and GG genotypes (p = 0.004).
Carrying of the C-allele IL6 -174G/C was detected in 71 patients (65.8%): CC in 15 (13.9%), GC in 56 (51.9%). There was a trend towards a decrease in GFR in patients with C-allele carriage (p = 0.068).
The prevalence of "unfavorable" alleles in patients with arterial hypertension and chronic kidney disease has been revealed. Thus, in patients with AH, the allele C of the AGT 704T/C gene was found in 75.6% of patients, the allele G of the NOS 894G/T gene – in 92.4%, the homozygous carriage of the alleles G and A of the IL1β -511G/A gene – in 57,1%, allele C of the gene IL6 -174G/C - in 65.4%. In patients with CKD, the C allele of the AGT gene was found in 78.0% of patients, the G gene of the NOS gene in 94.6%, the homozygous carrier of the G and A alleles of the IL1β gene – in 63.8%, the C allele of the IL6 gene – in 62,1%. Moreover, the majority of patients with arterial hypertension and CKD were carriers of three or four "unfavorable" allelic variants of the investigated genes.
CKD was diagnosed in 53% of cases, AH - in 74% of cases. Genotypes of endothelial dysfunction genes IL6 -174CC, IL1β -511 GG and AA were associated with CKD, AGT 704CC, NOS3 894GG-with AH. The T-allele AGT 704, the T-allele NOS3 894, the G allele of IL6 and the combination of the G and A alleles of IL1β had a protective effect.

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May 29, 2020

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