Альманах клинической медицины. 2021; 49: 142-148
Вклад полиморфизма генов AGT, GNB3, MTHFR, MTRR, ApoE, PPARα в развитие маскированной артериальной гипертензии у пациентов низкого и умеренного сердечно-сосудистого риска
https://doi.org/10.18786/2072-0505-2021-49-027Аннотация
Цель – определить вероятность развития маскированной артериальной гипертензии (МАГ) у пациентов низкого и умеренного сердечно-сосудистого риска (ССР) в зависимости от наличия полиморфизма некоторых генов.
Материал и методы. Девяносто двум пациентам (средний возраст 41,93±8,92 года) низкого и умеренного ССР без верифицированных сердечно-сосудистых заболеваний проведена оценка генотипов по маркерам AGT Thr174Met rs4762, GNB3 C825T rs5443, MTHFR C677T rs1801133, MTRR Ile22Met rs1801394, ApoE Cys130Arg rs 429358, PPARα G/C rs4253778, а также общеклиническое обследование и суточное мониторирование артериального давления (СМАД). В зависимости от наличия МАГ пациенты распределены в 2 группы: с впервые выявленной артериальной гипертензией, соответствующей критериям МАГ (n=58, 63%) и с нормальными показателями офисного и амбулаторного артериального давления, а также нормальными показателями артериального давления по данным СМАД (n=34, 37%).
Результаты. Группы не различались по возрасту, факторам ССР, сопутствующей патологии и клиническим характеристикам. В группе с МАГ оказалось статистически значимо больше мужчин, чем женщин (р=0,028). Среди пациентов с наличием МАГ наиболее значимым был генотип A/G полиморфизма Ile22Met rs1801394 гена MTRR: при оценке отношения шансов (ОШ) и относительного риска (ОР) развития МАГ показатели составили 4,23 и 2,17 соответственно (95% доверительный интервал (ДИ) для ОШ был 1,56–11,72; для ОР – 1,25–4,12). Статистически значимым оказался и генотип Т/С полиморфизма Cys130Arg rs 429358 гена АроЕ. Вероятность развития МАГ при генотипе Т/С по гену АроЕ увеличивалась более чем втрое: ОШ 3,67 (95% ДИ 1,34–10,28), ОР 2,15 (95% ДИ 1,17–4,36). При проведении корреляционного анализа выявлена прямая умеренная взаимосвязь наличия МАГ с полиморфизмами генов MTRR (Q=0,62) и АроЕ (Q=0,57).
Заключение. У пациентов низкого и умеренного ССР вероятность развития МАГ зависит не только от гендерных различий, но и от генетической детерминированности. Генамикандидатами для развития МАГ у таких пациентов служат генотипы A/G полиморфизма Ile22Met rs1801394 гена MTRR и Т/С полиморфизма Cys130Arg rs 429358 гена АроЕ.
Список литературы
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19. Wu S, Hsu LA, Teng MS, Lin JF, Chou HH, Lee MC, Wu YM, Su CW, Ko YL. Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population. Lipids Health Dis. 2016;15:94. doi: 10.1186/s12944-016- 0262-z.
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Almanac of Clinical Medicine. 2021; 49: 142-148
The contribution of the AGT, GNB3, MTHFR, MTRR, ApoE, and PPARα polymorphisms to the development of masked arterial hypertension in patients with low and moderate cardiovascular risk
https://doi.org/10.18786/2072-0505-2021-49-027Abstract
Aim: To assess the probability of masked arterial hypertension (MAH) in patients with low and moderate cardiovascular risk depending on polymorphisms in selected genes.
Materials and methods: Ninety two (92) patients (mean age, 41.93±8.92 years) with low and moderate cardiovascular risk without any documented cardiovascular disorders were assessed clinically and had 24-hour ECG monitoring performed, as well as genotyping on the following markers: AGT Thr174Met rs4762, GNB3 C825T rs5443, MTHFR C677T rs1801133, MTRR Ile22Met rs1801394, ApoE Cys130Arg rs 429358, and PPARα G/C rs4253778. Depending on the presence of MAH, the patients were divided into two groups: with newly diagnosed arterial hypertension corresponding to the MAH criteria (n=58, 63%) and with normal office-based and ambulatory blood pressure and normal blood pressure according to the results of 24-hour ECG monitoring (n=34, 37%).
Results: Two groups were not different by their age, cardiovascular risk factors, concomitant diseases and clinical characteristics. There were more men than women in the MAH group (р=0.028). In MAH patients, the most prevalent was Ile22Met rs1801394 A/G polymorphism of the MTRR gene (the odds ratio (OR) and relative risk (RR) for MAH were 4.23 [95% сonfidence interval (CI) 1.56–11.72] and 2.17 [1.25–4.12], respectively). The Cys130Arg rs 429358 Т/С genotype polymorphism of the АроЕ gene was also significant. The probability of MAH in the patients with АроЕ Т/С genotype was more than 3-fold higher: OR 3.67 [95% CI 1.34–10.28], RR 2.15 [95% CI 1.17–4.36]. The correlation analysis showed a moderate association between MAH and MTRR and АроЕ gene polymorphisms (Q=0.62 and Q=0.57, respectively).
Conclusion: In patients with low and moderate cardiovascular risk, the probability of MAH depends not only from their gender, but also from their genetic background. The candidate genes for MAH in such patients are Ile22Met rs1801394 A/G polymorphism of the MTRR gene and Cys130Arg rs 429358 Т/С polymorphism of the АроЕ gene.
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13. Semplicini A, Grandi T, Sandonà C, Cattelan A, Ceolotto G. G-Protein β3-Subunit Gene C825T Polymorphism and Cardiovascular Risk: An Updated Review. High Blood Press Cardiovasc Prev. 2015;22(3):225–232. doi: 10.1007/ s40292-015-0093-4.
14. Li WX, Dai SX, Zheng JJ, Liu JQ, Huang JF. Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency. Nutrients. 2015;7(8):6670– 6687. doi: 10.3390/nu7085303.
15. Wu H, Wang B, Ban Q, Chen L, Yan D, Yu Y, Song Y, Liu C, Cao J, Zhang J, Zhang Y, Zhang T, Zhang H, Guo H, Tang G, Zhang Y, Li J, Huo Y, Zang T, Qin X, Xu X. Association of total homocysteine with blood pressure in a general population of Chinese adults: a cross-sectional study in Jiangsu province, China. BMJ Open. 2018;8(6):e021103. doi: 10.1136/bmjopen-2017-021103.
16. Luo Z, Lu Z, Muhammad I, Chen Y, Chen Q, Zhang J, Song Y. Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis. Lipids Health Dis. 2018;17(1):191. doi: 10.1186/s12944-018- 0837-y.
17. Li WX, Lv WW, Dai SX, Pan ML, Huang JF. Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study. Lipids Health Dis. 2015;14:101. doi: 10.1186/s12944- 015-0099-x.
18. Zhen J, Huang X, Van Halm-Lutterodt N, Dong S, Ma W, Xiao R, Yuan L. ApoE rs429358 and rs7412 Polymorphism and Gender Differences of Serum Lipid Profile and Cognition in Aging Chinese Population. Front Aging Neurosci. 2017;9:248. doi: 10.3389/fnagi.2017.00248.
19. Wu S, Hsu LA, Teng MS, Lin JF, Chou HH, Lee MC, Wu YM, Su CW, Ko YL. Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population. Lipids Health Dis. 2016;15:94. doi: 10.1186/s12944-016- 0262-z.
20. Ruscica M, Busnelli M, Runfola E, Corsini A, Sirtori CR. Impact of PPAR-Alpha Polymorphisms – The Case of Metabolic Disorders and Atherosclerosis. Int J Mol Sci. 2019;20(18): 4378. doi: 10.3390/ijms20184378.
