GRK4 gene rs1801058 polymorphism and blood pressure response to acute salt loading test in newly diagnosed hypertension patients

doi:10.5246/jcps.2025.01.006

Journal of Chinese Pharmaceutical Sciences ›› 2025, Vol. 34 ›› Issue (1): 66-74.DOI: 10.5246/jcps.2025.01.006

• Drug administration and clinical pharmacy column • Previous Articles Next Articles

GRK4 gene rs1801058 polymorphism and blood pressure response to acute salt loading test in newly diagnosed hypertension patients

Xue Wang¹^,^#, Hongyi Wang²^,^#, Xinyi Zhang¹, Yan Tian³, Li Yang⁴, Xiaoxia Han⁵, Zhuo Wang³, Xiaoyan Nie¹, Ningling Sun²^,^*()

¹ Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
² Department of Hypertension, People's Hospital, Peking University, Beijing 100044, China
³ Beijing E-Seq Medical Technology Co. Ltd., Beijing 100192, China
⁴ Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650500, Yunnan, China
⁵ Qingxu County People's Hospital, Taiyuan 030400, Shanxi, China

Received:2024-08-21 Revised:2024-09-20 Accepted:2024-10-15 Online:2025-02-20 Published:2025-02-20
Contact: Ningling Sun
About author:
^# Xue Wang and Hongyi Wang have contributed equally and are co-first authors.

Abstract

Abstract:

G-protein coupled receptor kinase 4 (GRK4) gene plays a core role in renal dopamine D1 receptor function for handing renal sodium excretion, the rs1801058 T variant has ~50% frequency in the general East Asian population but lacks functional evidence for salt-sensitivity. In this prospective study, we identified rs1801058 genotypes by sequencing in hypertensives patients and analyzed the variant’s effects on blood pressure response to acute salt loading in 150 newly diagnosed hypertension patients. Our data indicated that there were no statistically significant difference in blood pressure changes between the overall rs1801058 genotype groups. Carriers of the C allele showed a significant rise in heart rate change according to acute saline loading. Among patients age ≤ 40year, T allele carriers showed higher changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) than C allele carriers when diuretic shrinkage. GRK4 single rs1801058 polymorphism cannot directly explain salt sensitivity in the Chinese hypertension patients.

Key words: GRK4, rs1801058, Salt-sensitivity, Blood pressure response

Supporting:

Xue Wang, Hongyi Wang, Xinyi Zhang, Yan Tian, Li Yang, Xiaoxia Han, Zhuo Wang, Xiaoyan Nie, Ningling Sun. GRK4 gene rs1801058 polymorphism and blood pressure response to acute salt loading test in newly diagnosed hypertension patients[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(1): 66-74.

Figures/Tables 5

References 21

[1]	Roth, G.A.; Mensah, G.A.; Johnson, C.O.; Addolorato, G.; Ammirati, E.; Baddour, L.M.; Barengo, N.C.; Beaton, A.Z.; Benjamin, E.J. ; Benziger, C.P.; Bonny, A.; Brauer, M.; Brodmann, M.; Cahill, T.J.; Carapetis, J.; Catapano, A.L.; Chugh, S.S.; Cooper, L.T.; Coresh, J.; Criqui, M.; DeCleene, N.; Eagle, K.A.; Emmons-Bell, S.; Feigin, V.L.; Fernández-Solà, J.; Fowkes, G.; Gakidou, E.; Grundy, S.M.; He, F.J.; Howard, G.; Hu, F.; Inker, L.; Karthikeyan, G.; Kassebaum, N.; Koroshetz, W.; Lavie, C.; Lloyd-Jones, D.; Lu, H.S.; Mirijello, A.; Temesgen, A.M.; Mokdad, A.; Moran, A.E.; Muntner, P.; Narula, J.; Neal, B.; Ntsekhe, M.; Moraes de Oliveira, G.; Otto, C.; Owolabi, M.; Pratt, M.; Rajagopalan,S.; Reitsma, M.; Ribeiro, A.L.P.; Rigotti, N.; Rodgers, A.; Sable, C.; Shakil, S.; Sliwa-Hahnle, K.; Stark, B.; Sundström, J.; Timpel, P.; Tleyjeh, I.M.; Valgimigli, M.; Vos, T.; Whelton, P.K.; Yacoub, M.; Zuhlke, L.; Murray, C.; Fuster, V.; Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J. Am. Coll. Cardiol. 2020, 7, 2982–3021.
[2]	World health statistics 2024: monitoring health for the SDGs, Sustainable Development Goals. Geneva: World Health Organization. 2024. Licence: CC BY-NC-SA 3.0 IGO.
[3]	Global report on hypertension: the race against a silent killer. Geneva: World Health Organization. 2023. Licence: CC BY-NC-SA 3.0 IGO.
[4]	He, J.; Gu, D.; Chen, J.; Jaquish, C.; Rao, D.; Hixson, J.; Chen, J.C.; Duan, X.; Huang, J.F.; Chen, C.S.; Kelly, T.; Bazzano, L.; Whelton, P. Gender difference in blood pressure responses to dietary sodium intervention in the GenSalt study. J. Hypertens. 2009, 27, 48–54.
[5]	Afolabi, J.; Laffer, C.L.; Beasley, H.K.; Hinton, A.; Masenga, S.K.; Kirabo, A. Salt Sensitivity of Blood Pressure. Circ. Res. 2024, 13, 1234–1239.
[6]	Kawasaki, T.; Delea, C.S.; Bartter, F.C.; Smith, H. The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension, Am. J. Med. 1978, 64, 193–198.
[7]	Kurtz, T.W.; DiCarlo, S.E.; Pravenec, M.; Morris, R.C.Jr. The American Heart Association Scientific Statement on salt sensitivity of blood pressure: Prompting consideration of alternative conceptual frameworks for the pathogenesis of salt sensitivity? J. Hyper. 2017, 35, 2214–2225.
[8]	Beheray, S.; Kansra,V.; Hussain, T.; Lokhandwala, M.F. Diminished natriuretic response to dopamine in old rats is due to an impaired D1-like receptor-signaling pathway. Kidney Int. 2000, 58, 712–720.
[9]	Sanada, H.; Yatabe, J.; Midorikawa, S.; Hashimoto, S.; Watanabe, T.; Moore, J.H.; Ritchie, M.D.; Williams, S.M.; Pezzullo, J.C.; Sasaki, M.; Eisner, G.M.; Jose, P.A.; Felder, R.A. Single-nucleotide polymorphisms for diagnosis of salt-sensitive hypertension. Clin. Chem. 2006, 52, 352–360.
[10]	Jose, P.A.; Eisner, G.M.; Felder, R.A. Role of dopamine receptors in the kidney in the regulation of blood pressure. Curr. Opin. Nephrol. Hypert. 2002, 11, 8–92.
[11]	Byrd, J.B. Personalized medicine and treatment approaches in hypertension: current perspectives. Integr. Blood Press. Contr. 2016, 59.
[12]	Vandell, A.G.; Lobmeyer, M.T.; Gawronski, B.E.; Langaee, T.Y.; Gong, Y.; Gums, J.G.; Beitelshees, A.L.; Turner, S.T.; Chapman, A.B.; Cooper-DeHoff, R.M.; Bailey, K.R.; Boerwinkle, E.; Pepine, C.J.; Liggett, S.B.; Johnson, J.A. G protein receptor kinase 4 polymorphisms: β-blocker pharmacogenetics and treatment-related outcomes in hypertension. Hypertension. 2012, 60, 957–964.
[13]	Hussain, T.; Lokhandwala, M.F. Renal dopamine DA1 receptor coupling with G(S) and G(q/11) proteins in spontaneously hypertensive rats. Am. J. Physiol. 1997, 272, F339–346.
[14]	Yang, J.; Hall, J.E.; Jose, P.A.; Chen, K.; Zeng, C.Y. Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics. Pharmacol. Ther. 2022, 239, 108194.
[15]	Premont, R.T.; MacRae, A.D.; Stoffel, R.H.; Chung, N.; Pitcher, J.A.; Ambrose, C.; Inglese, J.; MacDonald, M.E.; Lefkowitz, R.J. Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants. J. Biol. Chem. 1996, 271, 6403–6410.
[16]	N.C.f.B.I. (NCBI), "Single Nucleotide Polymorphism (SNP) rs1801058.", NCBI dbSNP Database. This data can be found online at https://www.ncbi.nlm.nih.gov/snp/rs1801058#frequency_tab.
[17]	Jiang, W.; Wang, X.; Li, R.P.; Wang, G. Shan, J.X.; Gu, M. Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang. PloS One. 2021, 16, e0255311.
[18]	Zhang, H.; Sun, Z.Q.; Liu, S.S.; Yang, L.N. Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis. Clin. Int. Aging. 2016, 11, 17–27.
[19]	Liu, C.; Xi, B. Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk. Int. J. Med. Sci. 2012, 9, 274–279.
[20]	Weinberger, M.H.; Miller, J.Z.; Luft, F.C.; Grim, C.E.; Fineberg, N.S. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986, 8, Ii127–134.
[21]	Muskalla, A.M.; Suter, P.M.; Saur, M.; Nowak, A.; Hersberger, M.; Krayenbuehl,P.-A. G-Protein Receptor Kinase 4 Polymorphism and Response to Antihypertensive Therapy. Clin. Chem. 2014, 60, 1543–1548.

GRK4 gene rs1801058 polymorphism and blood pressure response to acute salt loading test in newly diagnosed hypertension patients

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 5

References 21

Related Articles 0

Recommended Articles

Metrics

Comments