The efficacy of diuretics in complex treatment of patients with hypertension according to the Gly460Trp polymorphism of the α-adducin gene
DOI:
https://doi.org/10.14739/2310-1210.2021.4.225022Keywords:
hypertension, genetic polymorphism, genotyping, therapyAbstract
The aim of the study was to investigate the effect of thiazide diuretics on blood pressure (BP) depending on Gly460Trp ADD1 gene polymorphism in arterial hypertension (AH) patients of the Ukrainian population in order to predict their individual treatment
efficacy.
Material and methods. The study included 232 persons: 120 patients with verified stage II AH and 112 healthy individuals. Restriction fragment length polymerase chain reaction (PCR-RFLP) was used to detect genotype (the Gly460Trp-polymorphic locus of the ADD1 gene). The patients received standard therapy, which included ACE inhibitor – ramipril 5 mg, calcium channel antagonist – amlodipine 5 mg, statin – atorvastatin 20 mg, acetylsalicylic acid 75 mg. The patients were randomized into two groups: group I (60 persons) additionally taking treatment with 1.5 mg of indapamide retard and group II (60 persons) – with 25 mg of hydrochlorothiazide. The dynamic reduction of blood pressure has been assessed every 4 weeks for 2 months.
Results. Among 120 patients with AH, 91 persons (75.8 %) were homozygous for the G allele (GG), 26 persons (21.7 %) – heterozygous (GT) and 3 persons (2.5 %) – homozygous for the T allele (TT), while the G allele frequency in patients with hypertension was 0.87, and the T allele – 0.13. 98 healthy individuals (87.5 %) were homozygous for the G allele, 13 individuals (11.6 %) were heterozygous, and 1 person (0.9 %) was homozygous for the T allele. The carrier frequency of the G and T alleles was 0.93 and 0.07, respectively. Allelic distribution indicated the predominance of the G allele carriers by Gly460Trp polymorphism of the ADD1 gene among the Ukrainian population, regardless of whether AH symptoms were present. It is noteworthy that the number of the T allele carriers was 2 times large among symptomatic patients than that among healthy individuals. In patients with the T allele, the hypotensive efficacy of indapamide was almost 3 times higher than that in patients with the G allele. The antihypertensive effect of hydrochlorothiazide in patients with the GT and TT genotypes was 2 times greater than that in the GG genotype carriers depending on the presence of the T allele G460T polymorphism of ADD1 gene in the genotype.
Conclusions. Allelic distribution indicates the predominance of the G allele carriers by Gly460Trp ADD1 gene polymorphism among the Ukrainian population, regardless of whether AH symptoms are present. Among patients with AH, the accumulation of the T allele G460T polymorphic marker of the α-adducin gene is 2 times more than that in healthy individuals. Patients carrying the T allele demonstrate 2 times higher hypotensive efficacy of indapamide compared with hydrochlorothiazide.
References
Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D. L., Coca, A., de Simone, G., Dominiczak, A., Kahan, T., Mahfoud, F., Redon, J., Ruilope, L., Zanchetti, A., Kerins, M., Kjeldsen, S. E., Kreutz, R., Laurent, S., Lip, G., … ESC Scientific Document Group. (2018). 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European Heart Journal, 39(33), 3021-3104. https://doi.org/10.1093/eurheartj/ehy339
Ministry of Health of Ukraine. (2012, May 24). Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry arterialnii hipertenzii [On Approval and implementation of the technical medical documents on standardizing the management of arterial hypertension (No. 384)]. https://zakon.rada.gov.ua/laws/show/z0069-03
Zharinova, V. Yu., Shapovalenko, I. S., & Voynarovskaya, G. P. (2018). Prohnostychne znachennia osnovnykh faktoriv kardiovaskuliarnoho ryzyku u liudei z ishemichnoiu khvoroboiu sertsia vikom ponad 60 rokiv [Prognostic significance of the main cardiovascular risk factors in people with ischemic heart disease over 60 years of age]. Simeina medytsyna, (4), 70-73. https://doi.org/10.30841/2307-5112.4.2018.161073 [in Ukrainian].
Matyukha, L. F. (2016). Zastosuvannia diuretykiv u patsiientiv iz arterialnoiu hipertenziieiu: perspektyvy y obmezhennia [The use of diuretics in patients with arterial hypertension: perspectives and limitations]. Ukrainskyi medychnyi chasopys, (2), 33-36. [in Ukrainian].
Orlova, Ya. А., Kurlykina, N. V., & Seredenina, E. M. (2019). Tiazidnye i tiazidopodobnye diuretiki v terapii arterial'noi gipertenzii [Thiazide and Thiazide-Like Diuretics in Therapy of Arterial Hypertension]. Kardiologiya, 59(11), 84-94. https://doi.org/10.18087/cardio.2019.11.2653 [in Russian].
Semenkin, A. A., Zhivilova, L. A., Nechaeva, G. I., Chindareva, O. I., Loginova, E. N., & Pritykina T. V. (2016). Kontroliruemaya monoterapiya diuretikami u bol'nykh arterial'noi gipertoniei: effektivnost' i metabolicheskaya bezopasnost' [Controlled diuretic monotherapy in hypertensive patients: Efficiency and metabolic safety]. Terapevticheskii arkhiv, 88(9), 59-64. https://doi.org/10.17116/terarkh201688959-64 [in Russian].
Cameron, A. C., Lang, N. N., & Touyz, R. M. (2016). Drug Treatment of Hypertension: Focus on Vascular Health. Drugs, 76(16), 1529-1550. https://doi.org/10.1007/s40265-016-0642-8
McNally, R. J., Morselli, F., Farukh, B., Chowienczyk, P. J., & Faconti, L. (2019). A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective. British Journal of Clinical Pharmacology, 85(12), 2707-2713. https://doi.org/10.1111/bcp.14109
Roush, G. C., Abdelfattah, R., Song, S., Ernst, M. E., Sica, D. A., & Kostis, J. B. (2018). Hydrochlorothiazide vs chlorthalidone, indapamide, and potassium-sparing/hydrochlorothiazide diuretics for reducing left ventricular hypertrophy: A systematic review and meta-analysis. Journal of Clinical Hypertension, 20(10), 1507-1515. https://doi.org/10.1111/jch.13386
Asil, S., & Atalar, E. (2017). Hipertansiyon tedavisinde kullanılan tüm diüretikler aynı değildir. Türk Kardiyoloji Derneği Arşivi, 45(1), 94-101. https://doi.org/10.5543/tkda.2016.93137
Dubovyk, Ye. I., Harbuzova, V. Yu., & Ataman, A. V. (2016). G-1639A but Not C1173T VKORC1 Gene Polymorphism Is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population. BioMed Research International, 2016, Article 1298198. https://doi.org/10.1155/2016/1298198
Manunta, P., Ferrandi, M., Cusi, D., Ferrari, P., Staessen, J., & Bianchi, G. (2016). Personalized Therapy of Hypertension: the Past and the Future. Current Hypertension Reports, 18(3), Article 24. https://doi.org/10.1007/s11906-016-0632-y
Drobotya, N. V., Arutyunyan, L. V., & Pirozhenko, A. A. (2017). Rol' opredeleniya geneticheskogo polimorfizma v patogeneze arterial'noi gipertenzii s tsel'yu individualizatsii medikamentoznoi terapii [The role of the genetic polymorphism determination in arterial hypertension pathogenesis with the aim of individualization medical therapy]. Consilium Medicum, 19(5), 26-30. [in Russian].
Singh, M., Singh, A. K., Pandey, P., Chandra, S., Singh, K. A., & Gambhir, I. S. (2016). Molecular genetics of essential hypertension. Clinical and Experimental Hypertension, 38(3), 268-277. https://doi.org/10.3109/10641963.2015.1116543
Wei, L. K., Au, A., Teh, L. K., & Lye, H. S. (2016). Recent Advances in the Genetics of Hypertension. In M. S. Islam (Ed.). Hypertension: from basic research to clinical practice. Advances in Experimental Medicine and Biology (Vol. 956, pp. 561-581). Springer, Cham. https://doi.org/10.1007/5584_2016_75
Cooper-DeHoff, R. M., & Johnson, J. A. (2016). Hypertension pharmacogenomics: in search of personalized treatment approaches. Nature Reviews Nephrology, 12(2), 110-122. https://doi.org/10.1038/nrneph.2015.176
Oliveira-Paula, G. H., Pereira, S. C., Tanus-Santos, J. E., & Lacchini, R. (2019). Pharmacogenomics And Hypertension: Current Insights. Pharmacogenomics and Personalized Medicine, 12, 341-359. https://doi.org/10.2147/PGPM.S230201
Gupta, S., Jhawat, V., Agarwal, B. K., Roy, P., & Saini, V. (2019). Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension. Current Hypertension Reviews, 15(2), 123-134. https://doi.org/10.2174/1573402114666180731111453
Lanzani, C., Citterio, L., Glorioso, N., Manunta, P., Tripodi, G., Salvi, E., Carpini, S. D., Ferrandi, M., Messaggio, E., Staessen, J. A., Cusi, D., Macciardi, F., Argiolas, G., Valentini, G., Ferrari, P., & Bianchi, G. (2010). Adducin- and Ouabain-Related Gene Variants Predict the Antihypertensive Activity of Rostafuroxin, Part 2: Clinical Studies. Science Translational Medicine, 2(59), Article 59ra87. https://doi.org/10.1126/scitranslmed.3001814
Zhang, J. R., Hu, W. N., & Li, C. Y. (2019). A Review of the Epidemiological Evidence for Adducin Family Gene Polymorphisms and Hypertension. Cardiology Research and Practice, 2019, Article 7135604. https://doi.org/10.1155/2019/7135604
Ramu, P., Umamaheswaran, G., Shewade, D. G., Swaminathan, R. P., Balachander, J., & Adithan, C. (2010). Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk. Indian Journal of Human Genetics, 16(1), 8-15. https://doi.org/10.4103/0971-6866.64938
Shin, M. H., Chung, E. K., Kim, H. N., Park, K. S., Nam, H. S., Kweon, S. S., & Choi, J. S. (2004). Alpha-Adducin Gly460Trp Polymorphism and Essential Hypertension in Korea. Journal of Korean Medical Science, 19(6), 812-814. https://doi.org/10.3346/jkms.2004.19.6.812
Ishikawa, K., Katsuya, T., Sato, N., Nakata, Y., Takami, S., Takiuchi, S., Fu, Y., Higaki, J., & Ogihara, T. (1998). No Association Between α-Adducin 460 Polymorphism and Essential Hypertension in a Japanese Population. American Journal of Hypertension, 11(4), 502-506, https://doi.org/10.1016/S0895-7061(97)00486-X
Larson, N., Hutchinson, R., & Boerwinkle, E. (2000). Lack of Association of 3 Functional Gene Variants With Hypertension in African Americans. Hypertension, 35(6), 1297-1300. https://doi.org/10.1161/01.hyp.35.6.1297
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
