POLYMORPHIC VARIANTS OF G/C+915 TRANSFORMING GROWTH FACTOR BETA 1 AND ATRIAL FIBRILLATION IN PATIENTS WITH METABOLIC SYNDROME
https://doi.org/10.18705/1607-419X-2018-24-1-93-100
Abstract
Objective. Metabolic syndrome (MS) increases the risk of atrial fibrillation (AF). The probability of the incident AF increases in case of atrial fibrosis and remodeling. Transforming growth factor beta 1 (TGF-β1, encoding gene TGFB1) induces myocardial fibrosis, in particular, in the atria. We analyzed the distribution of CC, CG and GG genotypes G/C+915 polymorphism of TGFB1 gene in patients with MS and AF. Design and methods. We included 426 subjects (30–65 years old): 222 patients with MS, including 115 patients with paroxysmal and permanent AF. The control group included 209 healthy individuals without cardiovascular disease and metabolic disorders. Genomic DNA was isolated from the venous blood. Allelic variants were identified by polymerase chain reaction followed by restriction analysis with endonucleases BglI. Results. GG genotype G/C (+915) TGFB1 gene in patients with MS and AF is more frequent than in MS patients without AF (97,4 and 87,9 %, respectively; χ 2 = 6,19, p = 0,013) and in healthy individuals (97,4 and 86,6 %, respectively; χ 2 = 8,77, p = 0,003). GG genotype is associated with an increased the risk of AF in patients with MS (odds ratio (OR): 5,74, 95 % confidence interval (CI): 1,71–19,33, p = 0,012). There were no differences in GG genotype G/C (+915) TGFB1 gene in MS patients without AF and healthy individuals. GC genotype G/C (+915) TGFB1 gene in healthy individuals was found more frequently than in MS with AF (12,4 and 2,6 %, respectively; χ 2 = 7,63, p = 0,006) and more frequently in MS patients without AF (12,1 and 2,6 %, respectively; χ 2 = 6,19, p = 0,013). C allele (genotype GC+CC) gene TGFB1 is associated with the decreased risk of AF in patients with MS (OR = 0,19, 95 % CI 0,05–0,70, р = 0,001). Conclusions. We found an association of G/C (+915) TGFB1 gene with the risk of AF in patients with MS. C allele (СС and CG genotypes) seems to be protective and is associated with the 5,3-fold reduction in the risk of AF in patients with MS. We suggest that increased expression of gene TGFB1 causes heterogeneity of conduction and contributes to the AF in patients with MS.
About the Authors
Yi. Ma
First Pavlov State Medical University of St. Petersburg.
Russian Federation
Yi Ma, MD, PhD Student, Department of Therapy with the Course of Endocrinology, Cardiology and Functional Diagnostics. St. Petersburg.
Russian Federation
Yi Ma, MD, PhD Student, Department of Therapy with the Course of Endocrinology, Cardiology and Functional Diagnostics. St. Petersburg.
V. A. Ionin
First Pavlov State Medical University of St. Petersburg; Almazov National Medical Research Center.
Russian Federation
Russian Federation
Valery A. Ionin, MD, PhD, Assistant, Department of Therapy with the Course of Endocrinology, Cardiology and Functional Diagnostics; Researcher, Laboratory of Metabolic Syndrome.
St. Petersburg.
E. L. Zaslavskaya
First Pavlov State Medical University of St. Petersburg.
Russian Federation
Russian Federation
Ekaterina L. Zaslavskaya, MD, Assistant, Department of Therapy with the Course of Endocrinology, Cardiology and Functional Diagnostics.
St. Petersburg.
A. S. Ulitina
First Pavlov State Medical University of St. Petersburg; B. P. Konstantinov Petersburg Nuclear Physics Institute National Research Center “Kurchatov Institute”.
Russian Federation
Russian Federation
Anna S. Ulitina, PhD, Senior Researcher, Department of Molecular, Genetic and Nanobiotechnologies; Senior Researcher, Laboratory for Human Molecular Genetics.
St. Petersburg.
A. Panteleeva
First Pavlov State Medical University of St. Petersburg; B. P. Konstantinov Petersburg Nuclear Physics Institute National Research Center “Kurchatov Institute”.
Russian Federation
Aleksandra A. Panteleeva, Junior Researcher, Department of Molecular, Genetic and Nanobiotechnologies; Junior Researcher, Laboratory for Human Molecular Genetics.St. Petersburg.
Russian Federation
Aleksandra A. Panteleeva, Junior Researcher, Department of Molecular, Genetic and Nanobiotechnologies; Junior Researcher, Laboratory for Human Molecular Genetics.St. Petersburg.
O. D. Belyaeva
First Pavlov State Medical University of St. Petersburg; Almazov National Medical Research Center.
Russian Federation
Russian Federation
Olga D. Belyaeva, MD, PhD, DSc, Professor, Department of Therapy with the Course of Endocrinology, Cardiology and Functional Diagnostics, Head, Laboratory of Hypertension, Research Institution for Cardiovascular Diseases, Research Medical Scientific Centre; Leading Researcher, Laboratory of Metabolic Syndrome.
St. Petersburg.
S. N. Pchelina
First Pavlov State Medical University of St. Petersburg; B. P. Konstantinov Petersburg Nuclear Physics Institute National Research Center “Kurchatov Institute”.
Russian Federation
Russian Federation
Sofia N. Pchelina, Doctor of Biology Science, Acting Chief, Department of Molecular, Genetic and Nanobiotechnologies; Head, Laboratory for Human Molecular Genetics.
St. Petersburg.
E. I. Baranova
First Pavlov State Medical University of St. Petersburg; Almazov National Medical Research Center.
Russian Federation
Russian Federation
Elena I. Baranova, MD, PhD, DSc, Professor, Department of Therapy with the Course of Endocrinology, Cardiology and Functional Diagnostics, Director, Research Institution for Cardiovascular Diseases, Research Medical Scientific Centere; Chief, Laboratory of Metabolic Syndrome.
St. Petersburg.
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Review
For citations:
Ma Y., Ionin V.A., Zaslavskaya E.L., Ulitina A.S., Panteleeva A., Belyaeva O.D., Pchelina S.N., Baranova E.I. POLYMORPHIC VARIANTS OF G/C+915 TRANSFORMING GROWTH FACTOR BETA 1 AND ATRIAL FIBRILLATION IN PATIENTS WITH METABOLIC SYNDROME. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2018;24(1):93-100. (In Russ.) https://doi.org/10.18705/1607-419X-2018-24-1-93-100
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