Цель. Изучить взаимосвязь полиморфных вариантов rs1800470 гена трансформирующего ростового фактора β1 (TGF-β1) с тяжестью атеросклероза коронарных артерий (КА). Материал и методы. В исследование включено 256 больных ИМ (216 мужчин и 40 женщин) европеоидной расы в возрасте ≤65 лет (52,1±8,4). Геномную ДНК выделяли из венозной крови фенол-хлороформным методом. Полиморфизм rs1800470 гена TGF-β1 тестировали с помощью полимеразной цепной реакции (ПЦР) в режиме реального времени (зонды TaqMan, AB 7900HT). Оценка степени тяжести поражения коронарного русла производилась по протоколу стандартной полипроекционной коронароангиографии с расчетом индекса Gensini. Результаты. Впервые в сибирской популяции у мужчин доказана взаимосвязь аллеля А rs1800470 гена TGF-β1 с тяжестью коронарного атеросклероза. Носители аллеля А rs1800470 гена TGF-β1 имели отношение шансов (ОШ) многососудистого поражения КА (ОШ =2,84 (95% ДИ 1,37-5,87), p=0,004) и коронарного атеросклероза проксимального типа (ОШ =2,66 (95% ДИ 1,29-5,47), p=0,007). В целом индекс Gensini был значительно выше у носителей рискового аллеля А rs1800470 гена TGF-β1: генотип АА-57,33±41,89; генотип AG-52,86±40,74; генотип GG-43±28,83 (р>0,05), однако статистически значимыми различия были в верхней квартили (р=0,028). Риск тяжелого поражения КА (индекс Gensini >80 баллов) у носителей аллеля А rs1800470 гена TGF-β1 составило ОШ =3,64 (95% ДИ 1,06-12,49). У женщин статистически значимой взаимосвязи генотипа rs1800470 гена TGF-β1 с тяжестью поражения КА выявлено не было. Заключение. Аллель А rs1800470 гена TGF-β1 ассоциирован с тяжестью коронарного атеросклероза у мужчин.
Background. Coronary heart disease is the leading cause of death in the Russian Federation, causing social and economic damage to the state. Previously published studies showed the association of rs1800470 polymorphism of the gene of the transforming growth factor-β1 (TGF-β1) with the risk of developing coronary artery disease due to more severe atherosclerotic lesions of the coronary arteries. Aim of the research. To study the association of single-nucleotide polymorphism rs1800470 of the TGF-β1 gene with the rate of progression of atherosclerotic coronary artery lesion. Material and methods. The study included 89 men with myocardial infarction, a Caucasian race under the age of 65 years (51 ± 7.9). Genomic DNA was isolated from venous blood by the phenol-chloroform method. The rs1800470 polymorphism of the TGF-β1 gene was tested using real-time polymerase chain reaction (PCR) (TaqMan probes, AB 7900HT). Assessment of the severity of coronary lesion was carried out initially according to the standard polyprojection coronary angiography protocol with the Gensini score calculated, as well as in dynamics after 40.7 ± 29.7 months (from 5 to 103 months). Results. Carrier of the rs1800470 allele A of the TGF-β1 gene is an independent risk factor for coronary heart disease and is associated with a more aggressive course of coronary atherosclerosis in men: a 20 % worsening of the Gensini score was observed after 7 months (p = 0.013), and by 30 % after 5 months (p = 0.003) from the initial coronary angiography. In addition, the homozygous genotype AA rs1800470 of the TGF-β1 gene is associated with the development of late stent restenoses in this group of patients after 12 months of observation (p = 0.002). Conclusion. Identification of carriers of the rs1800470 allele A of the TGF-β1 gene can help identify patients at risk for more rapid progression of coronary artery atherosclerosis in order to conduct angiographic control in the early period – 6 months from the initial percutaneous coronary intervention.
Aim. To study the relationship between the angiographic dynamics of the state of the coronary bed in patients undergoing percutaneous coronary intervention (PCI) due to myocardial infarction (MI) and the carriage of polymorphic rs1800470 variants of the transforming growth factor beta-1 gene (TGF-β1).Material and methods. The study included 89 men with MI of the Caucasian race aged 32 to 65 years (52 [45,0-58,0]). Genomic deoxyribonucleic acid (DNA) was extracted from venous blood by phenol-chloroform technique. The rs1800470 polymorphism of the TGF-β1 gene was tested using real-time polymerase chain reaction (PCR) (TaqMan probes, AB 7900HT). Assessment of the severity of coronary lesions was carried out initially according to the standard coronary angiography (CAG) protocol with the calculation of the Gensini score. CAG was also conducted in the dynamics after 5-103 months (42,3±29,5 months) of the study beginning.Results. In male carriers of the rs1800470 A allele of the TGF-β1 gene, the mean values of the Gensini score statistically significantly increased (47,5±34,1 (CAG-1) and 64,5±35,5 (CAG-2), p <0,001) in comparison with carriers of the homozygous GG rs1800470 variant of the TGF-β1 gene (43,5±21,1 (CAG-1) and 46,2±23,2 (CAG2), p=0,066). In patients who had rs1800470 A allele of the TGF-β1 gene, a 20%decrease in the Gensini score was observed after 7 months (p=0,013), and 30% — after 5 months (p=0,003) of the initial CAG. The development of late stent restenoses in carriers of the rs1800470 A allele and the homozygous risk genotype AA of the TGF-β1 gene was noted at an earlier date — 8 (p=0,047) and 12 months (p=0,002), respectively.Conclusion. Currently, the conduct of CAG in dynamics in patients undergoing PCI is recommended as clinically indicated. The exception is the group of patients who underwent endoprosthesis replacement of the left coronary artery or have uncorrected stenosis of a different location from 3 to 12 months after PCI. The presented data show a possible predictor role of rG1800470 polymorphism of the TGF-β1 gene in relation to the progression of coronary atherosclerosis and the development of late stent restenoses.
The aim of the present study was to investigate the susceptibility of two coronary artery disease (CAD)-associated single nucleotide polymorphisms on 9p21 (rs1333049 and rs10757278) to myocardial infarction (MI) in a primary (stratification of high risk group for MI) and secondary prevention setting. The prospective observational study included 500 patients with MI [411 males (82.2%) and 89 females (17.8%)] under 65 years. The risk of MI for carriers of the homozygous CC genotype of rs1333049 and homozygous GG genotype of rs10757278 was 1.77 [95% confidence interval (CI): 1.36-2.37], and 1.70 (95% CI: 1.24-2.32) respectively. The risk of MI for heterozygous allele carriers was slightly lower. Specifically, the risk of MI was 1.58 (95% CI: 1.18-2.11) for both heterozygous and homozygous carriers of the rs1333049 C allele, and 1.36 (95% CI: 1.01-1.83) for the carriers of the rs10757278 G allele. A logistic regression model including sex, age, presence of excess weight or obesity, abdominal obesity, diabetes mellitus, arterial hypertension, hypercholesterolemia, positive family history and smoking status parameters revealed that rs1333049 CC genotype was an independent predictive factor of myocardial infraction [OR=1.71 (95% CI: 1.16-2.52), P=0.006]. Patients who underwent percutaneous coronary intervention (PCI) during index hospitalization and patients who did not receive PCI were followed up for two years after discharge. Compared with patients with MI who underwent PCI, the risk of recurrent acute coronary syndrome (re-ACS) was higher among rs1333049 C allele carriers who did not receive PCI during index hospitalization. One year after MI, the OR of re-ACS was 4.91 (95% CI: 1.45-16.66), while two years after MI, OR was 3.77 (95% CI: 1.50-9.52) in those patients who did not receive PCI during index hospitalization. There was no statistically significant association between polymorphic variants of rs1333049 and MI follow-up outcomes in patients who underwent PCI. The present study indicated clinical utility of 9p21.3 genotyping to predict the outcomes for patients with MI without PCI. Due to the small sample size, this association study forms basis for larger, nationwide studies investigating clinical applications of genetic data.
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