DOI: 10.18413/2658-6533-2023-9-1-0-2

**Polymorphic loci of AC026703.1 and HFE genes are associated with severe hypertension**

Background: Hypertension (HT) is characterized by high blood pressure (BP) and is one of the most common diseases in the world. At the moment, there is information in the literature about 1.5 thousand single-nucleotide polymorphic loci (SNP) associated with HP and BP according to genome – wide studies (GWAS). At the same time, replicative studies of GWAS significant genes in various populations, including Russian ones, are necessary. The aim of the study: To study the relationship of GWAS-significant polymorphic loci for HP with the stages of the disease. Materials and methods: For this study, two samples of patients with HT were formed: patients with stages 1-2 (n=384) and patients with stage 3 HT (n=555), and a control group of 466 people. For the experimental study, ten polymorphic loci of candidate genes associated with the development of HT were selected according to the data of GWAS conducted earlier. Associations were studied by the logistic regression method with a p_perm level <0.05. Results: The association of two GWAS significant candidate genes AC026703.1 (rs1173771) and HFE (rs1799945) with the risk of severe HT formation (stage 3 of the disease) was revealed. Allelic variant A rs1173771 (G/A) AC026703.1 has a protective value for the severe course of the disease (OR_dom=0.63 and 95%CI_dom 0.41-0.98 p_perm=0.048). The minor genotype GG rs1799945 (C/G) HFE significantly (more than 3 times) increases the risk of developing stage 3 HT (OR_rec=3.25 and 95%CI_rec 1.25-8.42 p_perm=0.017). Associations of GWAS significant of polymorphic loci for HT with the development of stages 1-2 of the disease have not been established. Conclusion: Polymorphisms rs1799945 of the HFE gene (OR=3.25) and rs1173771 of the AC026703.1 gene (OR=0.63) are associated with the risk of developing stage 3 HT.

Keywords: hypertension, polymorphism, association, GWAS.

Number of views: 833 (view statistics)

Количество скачиваний: 1279

Full text (HTML)Full text (PDF)To articles list

Information for citation:

Ivanova TA. Polymorphic loci of AC026703.1 and HFE genes are associated with severe hypertension. Research Results in Biomedicine. 2023;9(1):22-38 Russian. DOI: 10.18413/2658-6533-2023-9-1-0-2

User comments
Reference lists

While nobody left any comments to this publication.
You can be first.

Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021-3104. DOI: https://doi.org/10.1093/eurheartj/ehy339
Kobalava ZD, Konradi AO, Nedogoda SV, et al. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(3):3786. Russian. DOI: https://doi.org/10.15829/1560-4071-2020-3-3786
NCD Risk Factor Collaboration. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. The Lancet. 2017;389(10064):37-55. DOI: https://doi.org/10.1016/S0140-6736(16)31919-5
Chow CK, Teo KK, Rangarajan S, et al. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. Journal of the American Medical Association. 2013;310(9):959-968. DOI: https://doi.org/10.1001/jama.2013.184182
Zhou B, Perel P, Mensah GA, et al. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nature Reviews Cardiology. 2021;18(11):785-802. DOI: https://doi.org/10.1038/s41569-021-00559-8
Forouzanfar MH, Liu P, Roth GA, et al. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. Journal of the American Medical Association. 2017;317(2):165-182. DOI: https://doi.org/10.1001/jama.2016.19043
Evangelou E, Warren HR, Mosen-Ansorena D, et al. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nature Genetics. 2018;50(10):1412-1425. DOI: https://doi.org/10.1038/s41588-018-0205-x
Surendran P, Feofanova EV, Lahrouchi N, et al. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals. Nature Genetics. 2020;52(12):1314-1332. DOI: https://doi.org/10.1038/s41588-020-00713-x
Lip S, Padmanabhan S. Genomics of Blood Pressure and Hypertension: Extending the Mosaic Theory Toward Stratification. Canadian Journal of Cardiology. 2020;36(5):694-705. DOI: https://doi.org/10.1016/j.cjca.2020.03.001
Chen J, Wang W, Li Z, et al. Heritability and genome-wide association study of blood pressure in Chinese adult twins. Molecular genetics & genomic medicine. 2021;9(11):e1828. DOI: https://doi.org/10.1002/mgg3.1828
Padmanabhan S, Dominiczak AF. Genomics of hypertension: the road to precision medicine. Nature Reviews Cardiology. 2021;18:235-250. DOI: https://doi.org/10.1038/s41569-020-00466-4
Moskalenko M, Ponomarenko I, Reshetnikov E, et al. Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia. Scientific Reports. 2021;11(1):5224. DOI: https://doi.org/10.1038/s41598-021-84645-4
Takahashi Y, Yamazaki K, Kamatani Y, et al. A genome-wide association study identifies a novel candidate locus at the DLGAP1 gene with susceptibility to resistant hypertension in the Japanese population. Scientific Reports. 2021;11(1):19497. DOI: https://doi.org/10.1038/s41598-021-98144-z
Polonikov AV, Ushachev DV, Ivanov VP, et al. Altered erythrocyte membrane protein composition mirrors pleiotropic effects of hypertension susceptibility genes and disease pathogenesis. Journal of Hypertension. 2015;33(11):2265-2277. DOI: https://doi.org/10.1097/HJH.0000000000000699
Zhang H, Pushkarev B, Zhou J, et al. CACNA1C rs1006737 SNP increases the risk of essential hypertension in both Chinese Han and ethnic Russian people of Northeast Asia. Medicine. 2021;100(8):e24825. DOI: https://doi.org/10.1097/MD.0000000000024825
Bushueva O, Solodilova M, Churnosov M, et al. The Flavin-containing monooxygenase 3 gene and essential hypertension: the joint effect of polymorphism E158K and cigarette smoking on disease susceptibility. International Journal of Hypertension. 2014;2014:712169. DOI: https://doi.org/10.1155/2014/712169
Polonikov AV, Bushueva OY, Bulgakova IV, et al. A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility. Pharmacogenetics and Genomics. 2017;27(2):57-69. DOI: https://doi.org/10.1097/FPC.0000000000000261
Fan W, Qu X, Li J, et al. Associations between polymorphisms of the ADIPOQ gene and hypertension risk: a systematic and meta-analysis. Scientific Reports. 2017;7:41683. DOI: https://doi.org/10.1038/srep41683
Moskalenko MI, Milanova SN, Ponomarenko IV, et al. Study of associations of polymorphism of matrix metalloproteinases genes with the development of arterial hypertension in men. Kardiologiia. 2019;59(7S):31-39. Russian. DOI: https://doi.org/10.18087/cardio.2598
Polonikov A, Bykanova M, Ponomarenko I, et al. The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population. Clinical and Experimental Hypertension. 2017;39(4):306-311. DOI: https://doi.org/10.1080/10641963.2016.1246562
Alsamman AM, Almabrazi H, Zayed H. Whole-Genome Sequencing of 100 Genomes Identifies a Distinctive Genetic Susceptibility Profile of Qatari Patients with Hypertension. Journal of Personalized Medicine. 2022;12(5):722. DOI: https://doi.org/10.3390/jpm12050722
Bushueva OYu, Barysheva EM, Markov AV, et al. Molecular and epigenetic mechanisms of the involvement of redox-homeostasis genes in the development of various cardiovascular diseases. Medical Genetics. 2020;19(5):66-68. Russian. DOI: https://doi.org/10.25557/2073-7998.2020.05.66-68
Moskalenko MI, Ponomarenko IV, Polonikov AV, et al. Polymorphic locus rs652438 of the MMP12 gene is associated with the development of hypertension in women. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2019;25(1):60-65. Russian. DOI: https://doi.org/10.18705/1607-419X-2019-25-1-60-65
Lule SA, Mentzer AJ, Namara B, et al. A genome-wide association and replication study of blood pressure in Ugandan early adolescents. Molecular genetics & genomic medicine. 2019;7(10):e00950. DOI: https://doi.org/10.1002/mgg3.950
Kaur H, Crawford DC, Liang J, et al. Replication of European hypertension associations in a case-control study of 9,534 African Americans. PLoS ONE. 2021;16(11):e0259962. DOI: https://doi.org/10.1371/journal.pone.0259962
Soltész B, Pikó P, Sándor J, et al. The genetic risk for hypertension is lower among the Hungarian Roma population compared to the general population. PLoS ONE. 2020;15(6):e0234547. DOI: https://doi.org/10.1371/journal.pone.0234547
Althwab SA, Ahmed AA, Rasheed Z, et al. ATP2B1 genotypes rs2070759 and rs2681472 polymorphisms and risk of hypertension in Saudi population. Nucleosides, Nucleotides and Nucleic Acids. 2021;40(11):1075-1089. DOI: https://doi.org/10.1080/15257770.2021.1973034
Jamshidi J, Asnaashari A, Alipoor R, et al. ATP2B1 rs2681472 and STK39 rs35929607 polymorphisms and risk of Hypertension in Iranian Population. Medical Journal of the Islamic Republic of Iran. 2018;32:14. DOI: https://doi.org/10.14196/mjiri.32.14
Golovchenko OV. Molecular genetic determinants of pre-eclampsia. Research Results in Biomedicine. 2019;5(4):139-149. Russian. DOI: https://doi.org/10.18413/2658-6533-2019-5-4-0-11
Churnosov M, Abramova M, Reshetnikov E, et al. Polymorphisms of hypertension susceptibility genes as a risk factors of preeclampsia in the Caucasian population of central Russia. Placenta. 2022;129:51-61. DOI: https://doi.org/10.1016/j.placenta.2022.09.010
Ward LD, Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Research. 2016;44(D1):D877-D881. DOI: https://doi.org/10.1093/nar/gkv1340
Yarosh SL, Kokhtenko EV, Churnosov MI, et al. Joint effect of glutathione S-transferase genotypes and cigarette smoking on idiopathic male infertility. Andrologia. 2015;47(9):980-986. DOI: https://doi.org/10.1111/and.12367
Che R, Jack JR, Motsinger-Reif AA, et al. An adaptive permutation approach for genome-wide association study: evaluation and recommendations for use. BioData Mining. 2014;7:9. DOI: https://doi.org/10.1186/1756-0381-7-9
Ponomarenko IV, Polonikov AV, Churnosov MI. Association of ESR2 rs4986938 polymorphism with the development of endometrial hyperplasia. Obstetrics and Gynecology. 2019;4:66-72. Russian. DOI: https://dx.doi.org/10.18565/aig.2019.4.66-72
Dvornyk V. Integrated in-depth bioinformatic analysis suggests RELCH/KIAA1468, LINC02341, and AKAP11 as candidate genes for ages at menarche and menopause. Research Results in Biomedicine. 2021;7(3):220-231. DOI: https://doi.org/10.18413/2658-6533-2021-7-3-0-2
Talbert PB, Henikoff S. Histone variants at a glance. Journal of Cell Science. 2021;134(6):jcs244749. DOI: https://doi.org/10.1242/jcs.244749
Li Y, Wang Y, Zhang C, et al. ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways. Biochemical and Biophysical Research Communications. 2004;325(4):1383-1392. DOI: https://doi.org/10.1016/j.bbrc.2004.10.183
Liu C, Kraja AT, Smith JA, et al. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. Nature Genetics. 2016;48(10):1162-1170. DOI: https://doi.org/10.1038/ng.3660
Ehret GB, Ferreira T, Chasman DI, et al. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics. 2016;48(10):1171-1184. DOI: https://doi.org/10.1038/ng.3667
Hoffmann TJ, Ehret GB, Nandakumar P, et al. Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation. Nature Genetics. 2017;49(1):54-64. DOI: https://doi.org/10.1038/ng.3715
International Consortium for Blood Pressure Genome-Wide Association Studies, Ehret GB, Munroe PB, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011;478(7367):103-109. DOI: https://doi.org/10.1038/nature10405
Sung YJ, Winkler TW, de Las Fuentes L, et al. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. American Journal of Human Genetics. 2018;102(3):375-400. DOI: https://doi.org/10.1016/j.ajhg.2018.01.015
Wain LV, Vaez A, Jansen R, et al. Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney. Hypertension. 2017;70:e4-e19. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.117.09438
Surendran P, Drenos F, Young R, et al. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nature Genetics. 2016;48(10):1151-1161. DOI: https://doi.org/10.1038/ng.3654

All journals

Send article

Research Results in Biomedicine is included in the scientific database of the RINTs (license agreement No. 765-12/2014 dated 08.12.2014).

The journal is included in the list of peer-reviewed scientific publications recommended by the Higher Attestation Commission

The journal is indexed by the following scientific databases and platforms

Research Results in Biomedicine (ISSN 2658-6533)

The journal materials and website are licensed under Creative Commons «Attribution» 4.0 International.

The Founder: Federal State Autonomous Educational Institution of Higher Education "Belgorod National Research University"The Founder’s address: 85 Pobedy Street, Belgorod, the Belgorod region, 308015, Russia

The Publisher: Federal State Autonomous Educational Institution of HigherEducation "Belgorod National Research University" The Founder’s address:85 Pobedy Street, Belgorod, the Belgorod region, 308015, Russia

Editors Office: chief editor Mikhail I. Churnosov, e-mail: RR_MedPharm@bsuedu.ru, phone: +7 (4722) 30-14-03.

Regulations on the Journal

Certificate

Have questions?
You can write to us:

✉ Executive Secretary

✉ Site administration

✉ Content manager