Relationship Between GRK4 Polymorphisms and Essential Hypertension. A Study in A Group of Turkish Subjects

Hale Yıldız; Beki Kan; Oya Orun; Cevdet Nacar; Yüksel Doğan; Özlem Güneysel; Hulya Cabadak

doi:10.31067/acusaglik.1351877

Research Article

Relationship Between GRK4 Polymorphisms and Essential Hypertension. A Study in A Group of Turkish Subjects

Year 2024, Volume: 15 Issue: 1, 1 - 7, 31.01.2024

Hale Yıldız , Beki Kan , Oya Orun , Cevdet Nacar , Yüksel Doğan , Özlem Güneysel , Hulya Cabadak

https://doi.org/10.31067/acusaglik.1351877

Abstract

Background/Purpose:
G protein-coupled receptor kinase (GRK4) is associated with essential hypertension (EHT). GRK4 regulates sodium balance in the proximal tubules of the kidney. In this study, the possible roles of A142V and A486V polymorphisms in the development of hypertension were investigated in a Turkish population.
Methods: Genomic DNA was obtained from white blood cells using the standard DNA isolation kit (Roche). Genotypes of variants of GRK4 were determined by Polymerase chain reaction (PCR) - Restriction fragment length polymorphism (RFLP) analysis.
Results: In this study, GRKA142V and A486V polymorphisms were found to be associated with EHT in the Turkish population (P<0.05). The relationship between EHT and the A142V polymorphism was found to be more significant in men than in women.
Conclusion: Our results show that A142V and A486V polymorphisms of the GRK4 were associated with EHT in a Turkish population. As far as we know, this is the first study on the association between the GRK4 A142V and A486V gene polymorphisms and essential hypertension in the Turkish population. GRK4 could be a new therapeutic target for hypertension

Keywords

Gene polymorphism, metabolic disorders, cell signalling pathways

Ethical Statement

Etik kurul beyanı eklenmiştir

Supporting Institution

Marmara Üniversitesi

Project Number

Marmara University Scientific Research Projects Coordination Unit (Istanbul/Turkey) under grant number SAG-C-YLP-171209-0333

Thanks

This work has been supported by Marmara University Scientific Research Projects Coordination Unit. We would like to thank Ph.D. student Zehra Kanlı for the Graphical abstract and Fig.1-2 figure format preparation

References

1. Mancia G, De Backer G, Dominiczak A, et al. Hypertension E-ETFotMoA. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH- ESC Task Force on the Management of Arterial Hypertension. J Hypertens. 2007;25(9):1751-62. DOI:10.1097/HJH.0b013e3282f0580f.
2. Gu D, Su S, Ge D, et al. Association study with 33 single-nucleotide polymorphisms in 11 candidate genes for hypertension in Chinese. Hypertension. 2006;47(6):1147- 54.DOI:10.1161/01.HYP.0000219041.66702.45.
3. Jose PA, Soares-da-Silva P, Eisner GM, et al. Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. Biochim Biophys Acta. 2010;1802(12):1259-67.DOI: 10.1016/j.bbadis.2010.02.004.
4. Hussain T and Lokhandwala MF. Renal dopamine receptors and hypertension. Exp Biol Med (Maywood). 2003;228(2):134-42.DOI: 10.1177/153537020322800202. 5. Zeng C, Armando I, Luo Y, et al. Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice. Am J Physiol Heart Circ Physiol. 2008;294(2):H551-69.DOI: 10.1152/ajpheart.01036.2007.
6. Zeng C, Zhang M, Asico LD, et al. The dopaminergic system in hypertension. Clin Sci (Lond). 2007;112(12):583-97.DOI: 10.1042/CS20070018.
7. Speirs HJ, Katyk K, Kumar NN, et al. Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension. J Hypertens. 2004;22(5):931-36.DOI:1 0.1097/00004872-200405000- 00014.
8. Jose PA, Eisner GM, Felder RA. Dopamine and the kidney: a role in hypertension? Curr Opin Nephrol Hypertens. 2003;12(2):189-94. DOI:10.1097/00041552- 200303000-00010.
9. Zeng C, Villar VA, Eisner GM, et al. G protein-coupled receptor kinase 4: role in blood pressure regulation.Hypertension. 2008;51(6):1449-55.DOI: 10.1161/HYPERTENSIONAHA.107.096487.
10. Li L, Fu W, Gong X, et al. The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction. Eur Heart J. 2021;42(14):1415-30. DOI: 10.1093/eurheartj/ehaa878.
11. Sanada H, Yatabe J, Midorikawa S, et al. Amelioration of genetic hypertension by suppression of renal G protein-coupled receptor kinase type 4 expression. Hypertension. 2006;47(6):1131-39. DOI: 10.1161/01.HYP.0000222004.74872.17.
12. Felder RA and Jose PA. Mechanisms of disease: the role of GRK4 in the etiology of essential hypertension and salt sensitivity. Nat Clin Pract Nephrol. 2006;2(11):637-50. DOI: 10.1038/ncpneph0301. 13. Yang J, Hall JE, Jose PA, et al. Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics. Pharmacol Ther. 2022;239:108-94.DOI: 10.1016/j.pharmthera.2022.108194.
14. Harris RC. Abnormalities in renal dopamine signaling and hypertension: the role of GRK4. Curr Opin Nephrol Hypertens. 2012;21(1):61-5. DOI:10.1097/MNH.0b013e32834de2cb.
15. Wang Y, Li B, Zhao W, et al. Association study of G protein-coupled receptor kinase 4 gene variants with essential hypertension in northern Han Chinese. Ann Hum Genet. 2006;70(Pt 6):778-83.DOI: : 10.1111/j.1469-1809.2006.00278.x.
16. Felder RA, Sanada H, Xu J, et al. G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl Acad Sci U S A. 2002;99(6):3872-877.DOI: 10.1073/pnas.062694599.
17. Williams SM, Ritchie MD, Phillips JA, et al. Multilocus analysis of hypertension: a hierarchical approach. Hum Hered. 2004;57(1):28-38. DOI: 10.1159/000077387.
18. Martinez Cantarin MP, Ertel A, Deloach S, et al. Variants in genes involved in functional pathways associated with hypertension in African Americans. Clin Transl Sci. 2010;3(6):279-86. DOI: 10.1111/j.1752-8062.2010.00242.x.
19. Bengra C, Mifflin TE, Khripin Y, et al. Genotyping of essential hypertension single- nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primers. Clin Chem. 2002;48(12):2131-40. PMID: 12446468.
20. Zhu H, Lu Y, Wang X, et al. The G protein-coupled receptor kinase 4 gene modulates stress-induced sodium excretion in black normotensive adolescents. Pediatr Res. 2006;60(4):440-42. 21. Zhu H, Lu Y, Wang X, Treiber FA, et al. The G protein-coupled receptor kinase 4 gene affects blood pressure in young normotensive twins. Am J Hypertens. 2006;19(1):61-66.DOI: 10.1203/01.pdr.0000238250.64591.44. Epub 2006 Aug 28.
22. Asbarinsyah NA, Candrasatria RM, Widyantoro B, et al. 2 Association between Salt Sensitive-Related Gene Polymorphism and Hypertension in Rural Indonesian Sundanese Population. Journal of Hypertension. 2019;37 p e1, July 2019.DOI: 10.1097/01.hjh.0000579484.14389.fb

Year 2024, Volume: 15 Issue: 1, 1 - 7, 31.01.2024

Hale Yıldız , Beki Kan , Oya Orun , Cevdet Nacar , Yüksel Doğan , Özlem Güneysel , Hulya Cabadak

https://doi.org/10.31067/acusaglik.1351877

Abstract

Project Number

Marmara University Scientific Research Projects Coordination Unit (Istanbul/Turkey) under grant number SAG-C-YLP-171209-0333

References

1. Mancia G, De Backer G, Dominiczak A, et al. Hypertension E-ETFotMoA. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH- ESC Task Force on the Management of Arterial Hypertension. J Hypertens. 2007;25(9):1751-62. DOI:10.1097/HJH.0b013e3282f0580f.
2. Gu D, Su S, Ge D, et al. Association study with 33 single-nucleotide polymorphisms in 11 candidate genes for hypertension in Chinese. Hypertension. 2006;47(6):1147- 54.DOI:10.1161/01.HYP.0000219041.66702.45.
3. Jose PA, Soares-da-Silva P, Eisner GM, et al. Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. Biochim Biophys Acta. 2010;1802(12):1259-67.DOI: 10.1016/j.bbadis.2010.02.004.
4. Hussain T and Lokhandwala MF. Renal dopamine receptors and hypertension. Exp Biol Med (Maywood). 2003;228(2):134-42.DOI: 10.1177/153537020322800202. 5. Zeng C, Armando I, Luo Y, et al. Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice. Am J Physiol Heart Circ Physiol. 2008;294(2):H551-69.DOI: 10.1152/ajpheart.01036.2007.
6. Zeng C, Zhang M, Asico LD, et al. The dopaminergic system in hypertension. Clin Sci (Lond). 2007;112(12):583-97.DOI: 10.1042/CS20070018.
7. Speirs HJ, Katyk K, Kumar NN, et al. Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension. J Hypertens. 2004;22(5):931-36.DOI:1 0.1097/00004872-200405000- 00014.
8. Jose PA, Eisner GM, Felder RA. Dopamine and the kidney: a role in hypertension? Curr Opin Nephrol Hypertens. 2003;12(2):189-94. DOI:10.1097/00041552- 200303000-00010.
9. Zeng C, Villar VA, Eisner GM, et al. G protein-coupled receptor kinase 4: role in blood pressure regulation.Hypertension. 2008;51(6):1449-55.DOI: 10.1161/HYPERTENSIONAHA.107.096487.
10. Li L, Fu W, Gong X, et al. The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction. Eur Heart J. 2021;42(14):1415-30. DOI: 10.1093/eurheartj/ehaa878.
11. Sanada H, Yatabe J, Midorikawa S, et al. Amelioration of genetic hypertension by suppression of renal G protein-coupled receptor kinase type 4 expression. Hypertension. 2006;47(6):1131-39. DOI: 10.1161/01.HYP.0000222004.74872.17.
12. Felder RA and Jose PA. Mechanisms of disease: the role of GRK4 in the etiology of essential hypertension and salt sensitivity. Nat Clin Pract Nephrol. 2006;2(11):637-50. DOI: 10.1038/ncpneph0301. 13. Yang J, Hall JE, Jose PA, et al. Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics. Pharmacol Ther. 2022;239:108-94.DOI: 10.1016/j.pharmthera.2022.108194.
14. Harris RC. Abnormalities in renal dopamine signaling and hypertension: the role of GRK4. Curr Opin Nephrol Hypertens. 2012;21(1):61-5. DOI:10.1097/MNH.0b013e32834de2cb.
15. Wang Y, Li B, Zhao W, et al. Association study of G protein-coupled receptor kinase 4 gene variants with essential hypertension in northern Han Chinese. Ann Hum Genet. 2006;70(Pt 6):778-83.DOI: : 10.1111/j.1469-1809.2006.00278.x.
16. Felder RA, Sanada H, Xu J, et al. G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl Acad Sci U S A. 2002;99(6):3872-877.DOI: 10.1073/pnas.062694599.
17. Williams SM, Ritchie MD, Phillips JA, et al. Multilocus analysis of hypertension: a hierarchical approach. Hum Hered. 2004;57(1):28-38. DOI: 10.1159/000077387.
18. Martinez Cantarin MP, Ertel A, Deloach S, et al. Variants in genes involved in functional pathways associated with hypertension in African Americans. Clin Transl Sci. 2010;3(6):279-86. DOI: 10.1111/j.1752-8062.2010.00242.x.
19. Bengra C, Mifflin TE, Khripin Y, et al. Genotyping of essential hypertension single- nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primers. Clin Chem. 2002;48(12):2131-40. PMID: 12446468.
20. Zhu H, Lu Y, Wang X, et al. The G protein-coupled receptor kinase 4 gene modulates stress-induced sodium excretion in black normotensive adolescents. Pediatr Res. 2006;60(4):440-42. 21. Zhu H, Lu Y, Wang X, Treiber FA, et al. The G protein-coupled receptor kinase 4 gene affects blood pressure in young normotensive twins. Am J Hypertens. 2006;19(1):61-66.DOI: 10.1203/01.pdr.0000238250.64591.44. Epub 2006 Aug 28.
22. Asbarinsyah NA, Candrasatria RM, Widyantoro B, et al. 2 Association between Salt Sensitive-Related Gene Polymorphism and Hypertension in Rural Indonesian Sundanese Population. Journal of Hypertension. 2019;37 p e1, July 2019.DOI: 10.1097/01.hjh.0000579484.14389.fb

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Details

Primary Language	English
Subjects	Biochemistry and Cell Biology (Other)
Journal Section	Research Articles
Authors	Hale Yıldız 0009-0005-9041-0496 Beki Kan 0000-0002-2738-9680 Oya Orun 0000-0003-1581-2207 Cevdet Nacar 0000-0002-8293-1495 Yüksel Doğan 0009-0004-0538-2068 Özlem Güneysel 0000-0002-1833-2199 Hulya Cabadak 0000-0001-5757-2198
Project Number	Marmara University Scientific Research Projects Coordination Unit (Istanbul/Turkey) under grant number SAG-C-YLP-171209-0333
Publication Date	January 31, 2024
Submission Date	August 31, 2023
Published in Issue	Year 2024Volume: 15 Issue: 1

Cite

EndNote	Yıldız H, Kan B, Orun O, Nacar C, Doğan Y, Güneysel Ö, Cabadak H (January 1, 2024) Relationship Between GRK4 Polymorphisms and Essential Hypertension. A Study in A Group of Turkish Subjects. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 15 1 1–7.

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