Home mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population
Article
Licensed
Unlicensed Requires Authentication

mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population

  • Varsha Varakantham , Ashok Kumar Kurakula Sailoo , Balakrishna Nagalla and Dinesh Kumar Bharatraj EMAIL logo
Published/Copyright: May 11, 2018
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 8

Abstract

Background:

β1-Adrenoreceptor (ADRB1) genetic polymorphisms are widely studied for susceptibility to many cardiovascular diseases such as essential hypertension. However, the mRNA expression of ADRB1 is rarely studied.

Methods:

A case-control pilot study with 292 hypertensives and 324 controls was designed to evaluate the role of the Ser49Gly and Arg389Gly, which are commonly studied single nucleotide polymorphisms (SNP), in the mRNA levels of ADRB1, in conjunction with its genetic predisposition to essential hypertension.

Results:

Differential expression of ADRB1 mRNA was seen between hypertensives and controls (p<0.01) based on genetic variants of Ser49Gly. Among hypertensive subjects, Ser49Ser and Gly49Gly were highly expressed in comparison to Ser49Gly (p<0.05 and p<0.01, respectively), whereas genetic variants of Arg389Gly did not demonstrate any such variations. We found no association between the ADRB1 SNPs viz., Ser49Gly and Arg389Gly and essential hypertension.

Conclusions:

The increased mRNA levels of Gly49Gly may indicate a plausible role in the interindividual variations in drug response. Further, ADRB1 polymorphisms did not contribute to the genetic risk of essential hypertension. Studies with larger sample size are warranted to confirm these observations in the South Indian population.

Keywords: ADRB1; Arg389Gly; essential hypertension; mRNA expression; Ser49Gly; SNPs
Corresponding author: Dr. Dinesh Kumar Bharatraj, Scientist ‘F’, Food and Drug Toxicology Research Centre, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, Telangana, India, Mobile: 09849082088, Phone: +91-40-27197322, Fax: +91-40-27019074

Acknowledgments

We are grateful to the Department of Science and Technology (DST) for according Inspire fellowship (Registration no.: IF110472) and thankful to NIN (Indian Council of Medical Research) for the facility to work (Project no.: 12FD-10). We also acknowledge the support of Gandhi Medical College, Hyderabad, India. We appreciate Mr. Nishanth Kumar for his contribution in sample collection and Ms. Kiranmayee Ale in sample processing.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Brodde OE, Michel MC. Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev 1999;51:651–90.Search in Google Scholar

2. Nieminen T, Lehtimäki T, Laiho J, Rontu R, Niemelä K, Kööbi T, et al. Effects of polymorphisms in β1-adrenoceptor and α-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study. J Appl Physiol 2006;100:507–11.10.1152/japplphysiol.00899.2005Search in Google Scholar PubMed

3. Ramu P, Rajan S, Shewade D, Swaminathan R, Dutta T, Balachander J, et al. Genetic variants of β1-adrenoceptor gene polymorphisms (Ser49gly and Arg389gly) and essential hypertension in a south Indian Tamil Population. Clin Exp Pharmacol Physiol 2009;36:576–82.10.1111/j.1440-1681.2008.05117.xSearch in Google Scholar PubMed

4. Wang H, Liu J, Liu K, Liu Y, Wang Z, Lou Y, et al. β1-Adrenoceptor gene Arg389Gly polymorphism and essential hypertension risk in general population: a meta-analysis. Mol Biol Rep 2013;40:4055–63.10.1007/s11033-012-2483-1Search in Google Scholar PubMed

5. Kong H, Li X, Zhang S, Guo S, Niu W. The β1-adrenoreceptor gene Arg389Gly and Ser49Gly polymorphisms and hypertension: a meta-analysis. Mol Biol Rep 2013;40:4047–53.10.1007/s11033-012-2482-2Search in Google Scholar PubMed

6. Mason DA, Moore JD, Green SA, Liggett SB. A gain-of- function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem 1999;274:12670–4.10.1074/jbc.274.18.12670Search in Google Scholar PubMed

7. Levin MC, Marullo S, Muntaner O, Andersson B, Magnusson Y. The myocardium-protective Gly-49 variant of the beta1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem 2002;277:30429–35.10.1074/jbc.M200681200Search in Google Scholar PubMed

8. Rathz DA, Brown KM, Kramer LA, Liggett SB. Amino acid 49 polymorphisms of the human beta1-adrenergic receptor affect agonist-promoted trafficking. J Cardiovasc Pharmacol 2002;39:155–60.10.1097/00005344-200202000-00001Search in Google Scholar PubMed

9. Iemitsu M, Miyauchi T, Maeda S, Sakai S, Kobayashi T, Fujii N, et al. Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat. Am J Physiol Regul Integr Comp Physiol 2001;281:R2029–36.10.1152/ajpregu.2001.281.6.R2029Search in Google Scholar PubMed

10. Oliver E, Rovira E, Montó F, Valldecabres C, Julve R, Muedra V, et al. β-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion. J Hypertens 2010;28:1281–9.10.1097/HJH.0b013e3283383564Search in Google Scholar PubMed

11. Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction: twenty-something years on. Nat Protoc 2006;1:581–5.10.1038/nprot.2006.83Search in Google Scholar PubMed

12. Masek T, Vopalensky V, Suchomelova P, Pospisek M. Denaturing RNA electrophoresis in TAE agarose gels. Anal Biochem 2005;336:46–50.10.1016/j.ab.2004.09.010Search in Google Scholar

13. Yuan JS, Reed A, Chen F, Stewart CN Jr. Statistical analysis of real-time PCR data. BMC Bioinformatics 2006;7:85–96.10.1186/1471-2105-7-85Search in Google Scholar

14. Bristow MR. Why does the myocardium fail? Insights from basic science. Lancet 1998;352:SI8–4.10.1016/S0140-6736(98)90311-7Search in Google Scholar

15. Bristow MR. Mechanistic and clinical rationales for using beta-blockers in heart failure. J Card Fail 2000;6:8–14.Search in Google Scholar

16. Naga Prasad SV, Nienaber J, Rockman HA. Beta-adrenergic axis and heart disease. Trends Genet 2001;17:S44–9.10.1016/S0168-9525(01)02487-8Search in Google Scholar

17. Wyss JM. The role of the sympathetic nervous system in hypertension. Curr Opin Nephrol Hypertens 1993;2:265–73.10.1097/00041552-199303000-00014Search in Google Scholar

18. Mysliveček J, Nováková M, Palkovits M, Krizǎnová O, Kvetňanský R. Distribution of mRNA and binding sites of adrenoceptors and muscarinic receptors in the rat heart. Life Sci 2006;79:112–20.10.1016/j.lfs.2005.12.026Search in Google Scholar

19. Giltrow E, Eccles PD, Hutchinson TH, Sumpter JP, Rand-Weaver M. Characterisation and expression of β1-, β2- and β3-adrenergic receptors in the fathead minnow (Pimephales promelas). Gen Comp Endocrinol 2011;173:483–90.10.1016/j.ygcen.2011.07.006Search in Google Scholar

20. Liu H, Xing X, Huang L, Huang Z, Yuan H. The expression level of myocardial β1-adrenergic receptor affects metoprolol antihypertensive effects: a novel mechanism for interindividual difference. Med Hypotheses 2013;81:71–2.10.1016/j.mehy.2013.02.014Search in Google Scholar

21. Dungan JR, Conley YP, Langaee TY, Johnson JA, Kneipp SM, Hess PJ, et al. Altered beta-2 adrenergic receptor gene expression in human clinical hypertension. Biol Res Nurs 2010;11:17–26.10.1177/1099800409332538Search in Google Scholar

22. Matsuda N, Hattori Y, Gando S, Akaishi Y, Kemmotsu O, Kanno M. Diabetes-induced down-regulation of beta1-adrenoceptor mRNA expression in rat heart. Biochem Pharmacol 1999;58:881–5.10.1016/S0006-2952(99)00164-1Search in Google Scholar

23. Kay LJ, Rostami-Hodjegan A, Suvarna SK, Peachell PT. Influence of β2-adrenoceptor gene polymorphisms on β2-adrenoceptor-mediated responses in human lung mast cells. Br J Pharmacol 2009;152:323–31.10.1038/sj.bjp.0707400Search in Google Scholar

24. Mak JC, Nishikawa M, Haddad EB, Kwon OJ, Hirst SJ, Twort CH, et al. Localisation and expression of β-adrenoceptor subtype mRNAs in human lung. Eur J Pharmacol 1996;302:215–21.10.1016/0014-2999(96)00104-5Search in Google Scholar

25. Shu J, Wen G, Liu H, Zhong J, Chen Z, Huang L, et al. Relationship between the β1-adrenergic receptor and the β2-adrenergic receptor in hypertension. Int J Clin Exp Pathol 2017;10:3949–56.Search in Google Scholar

26. Berkowitz DE, Nardone NA, Smiley RM, Price DT, Kreutter DK, Fremeau RT, et al. Distribution of beta 3-adrenoceptor mRNA in human tissues. Eur J Pharmacol 1995;289:223–8.10.1016/0922-4106(95)90098-5Search in Google Scholar

27. Rathz DA, Gregory KN, Fang Y, Brown KM, Liggett SB. Hierarchy of polymorphic variation and desensitization permutations relative to beta 1- and beta 2-adrenergic receptor signaling. J Biol Chem 2003;278:10784–9.10.1074/jbc.M206054200Search in Google Scholar PubMed

28. Liu J, Liu Z, Yu B, Xu F, Mo W, Zhou G, et al. β1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther 2006;80:23–32.10.1016/j.clpt.2006.03.004Search in Google Scholar PubMed

29. Filigheddu F, Reid JE, Troffa C, PinnaParpaglia P, Argiolas G, Testa A, et al. Genetic polymorphisms of the β-adrenergic system: association with essential hypertension and response to β-blockade. Pharmacogenomics J 2004;4:154–60.10.1038/sj.tpj.6500247Search in Google Scholar PubMed

30. Ramu P, Rajan S, Shewade D, Swaminathan R, Dutta T, Balachander J, et al. Genetic variants of β1-adrenoceptor gene polymorphisms (Ser49gly And Arg389gly) and essential hypertension in a South Indian Tamil population. Clin Exp Pharmacol Physiol 2009;36:576–82.10.1111/j.1440-1681.2008.05117.xSearch in Google Scholar PubMed

31. Hu R, Zhao S, Niu G, Zhang C, Wang Z, Jiang M. Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population. Neural Regen Res 2006;1:226–9.Search in Google Scholar

32. Gjesing AP, Andersen G, Albrechtsen A, Glümer C, Borch-Johnsen K, Jørgensen T, et al. Studies of associations between the Arg389Gly polymorphism of the β1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. Diabet Med 2007;24:392–7.10.1111/j.1464-5491.2006.02031.xSearch in Google Scholar PubMed

33. Shioji K, Kokubo Y, Mannami T, Inamoto N, Morisaki H, Mino Y, et al. Association between hypertension and the alpha-adducin, beta1-adrenoreceptor, and G-protein beta3 subunit genes in the Japanese population; the Suita study. Hypertens Res 2004;27:31–7.10.1291/hypres.27.31Search in Google Scholar PubMed

34. Johnson AD, Newton-cheh C, Chasman DI, Ehret GB, Rose L, Rice K, et al. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals. Hypertension 2011;57:903–10.10.1161/HYPERTENSIONAHA.110.158667Search in Google Scholar PubMed PubMed Central

35. Peng Y, Xue H, Luo L, Yao W, Li R. Polymorphisms of the β1-adrenergic receptor gene are associated with essential hypertension in Chinese. Clin Chem Lab Med 2009;47:1227–31.10.1515/CCLM.2009.276Search in Google Scholar PubMed

36. Bengtsson K, Melander O, Orho-melander M, Lindblad U, Ranstam J, Groop L. Polymorphism in the Beta1-adrenergic receptor gene and hypertension. Circulation 2001;104:187–90.10.1161/01.CIR.104.2.187Search in Google Scholar

37. Kitsios GD, Zintzaras E. Synopsis and data synthesis of genetic association studies in hypertension for the adrenergic receptor family genes: the CUMAGAS-HYPERT Database. Am J Hypertens 2010;23:305–13.10.1038/ajh.2009.251Search in Google Scholar PubMed PubMed Central

38. Li Y, Li N, Yang L, Li Y, Ding X, Zhao H, et al. Polymorphisms of Arg389Gly of β1-adrenergic receptor gene and essential hypertension risk: a meta analysis. Zhonghua Yi Xue Za Zhi 2011;91:3115–9.Search in Google Scholar

39. rs1801252- (SNP) – Population genetics – Homo sapiens – Ensembl genome browser 85 [Internet]. Available from: https://www.ensembl.org/Homo_sapiens/Variation/Population?r=10:114043777-114044777;v=rs1801252;vdb=variation;vf=1243287.Search in Google Scholar

40. rs1801253- (SNP) – Population genetics – Homo sapiens – Ensembl genome browser 85 [Internet]. Available from: https://www.ensembl.org/Homo_sapiens/Variation/Explore?db=core;r=10:114044797-114045797;v=rs1801253;vdb=variation;vf=1243288.Search in Google Scholar

41. Hesse C, Eisenach JH. Genetic variation in the Beta(2)- adrenergic receptor: impact on intermediate cardiovascular phenotypes. Curr Pharmacogenomics Person Med 2008;6: 160–70.10.2174/1875692110806030160Search in Google Scholar PubMed PubMed Central

42. Kunes J, Kadlecova M, Zicha J. Gene–environment interactions: their role in hypertension development. In: Ostadal B, Nagano M, Dhalla N, editors. Genes and cardiovascular function. Boston, MA: Springer, 2011.Search in Google Scholar

43. Taylor JY, Sun YV, Hunt SC, Kardia SL. Gene-environment interaction for hypertension among African American women across generations. Biol Res Nurs 2010;12:149–55.10.1177/1099800410371225Search in Google Scholar PubMed PubMed Central

Received: 2017-10-01
Accepted: 2017-12-05
Published Online: 2018-05-11
Published in Print: 2018-07-26

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Procalcitonin for diagnosing and monitoring bacterial infections: for or against?
  4. Is it time to abandon the Nobel Prize?
  5. In Memoriam
  6. Norbert Tietz, 13th November 1926–23rd May 2018
  7. Reviews
  8. Procalcitonin guidance in patients with lower respiratory tract infections: a systematic review and meta-analysis
  9. Telomere biology and age-related diseases
  10. Opinion Paper
  11. Procalcitonin-guided antibiotic therapy: an expert consensus
  12. Genetics and Molecular Diagnostics
  13. mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population
  14. General Clinical Chemistry and Laboratory Medicine
  15. External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact
  16. Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes
  17. Observational studies on macroprolactin in a routine clinical laboratory
  18. Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results
  19. Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility
  20. Hematology and Coagulation
  21. Analytical performance of an automated volumetric flow cytometer for quantitation of T, B and natural killer lymphocytes
  22. Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity
  23. Reference Values and Biological Variations
  24. Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women
  25. Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects
  26. Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents
  27. Cancer Diagnostics
  28. Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations
  29. Cardiovascular Diseases
  30. Clinical performance of a new point-of-care cardiac troponin I test
  31. Diabetes
  32. Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early β-cell function impairment
  33. Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods
  34. Infectious Diseases
  35. Serum procalcitonin concentration within 2 days postoperatively accurately predicts outcome after liver resection
  36. Predictive value of serum gelsolin and Gc globulin in sepsis – a pilot study
  37. Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis
  38. Letter to the Editor
  39. Glucose and total protein: unacceptable interference on Jaffe creatinine assays in patients
  40. Interference of glucose and total protein on Jaffe-based creatinine methods: mind the covolume
  41. Interference of glucose and total protein on Jaffe based creatinine methods: mind the covolume – reply
  42. Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia
  43. Paraprotein interference in the diagnosis of hepatitis C infection
  44. Timeo apis mellifera and dona ferens: bee sting-induced Kounis syndrome
  45. Bacterial contamination of reusable venipuncture tourniquets in tertiary-care hospital
  46. Detection of EDTA-induced pseudo-leukopenia using automated hematology analyzer with VCS technology
  47. Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis
  48. Thromboelastometry reveals similar hemostatic properties of purified fibrinogen and a mixture of purified cryoprecipitate protein components
  49. Bicarbonate interference on cobas 6000 c501 chloride ion-selective electrodes
https://doi.org/10.1515/cclm-2017-0882
Keywords for this article
ADRB1; Arg389Gly; essential hypertension; mRNA expression; Ser49Gly; SNPs

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Procalcitonin for diagnosing and monitoring bacterial infections: for or against?
  4. Is it time to abandon the Nobel Prize?
  5. In Memoriam
  6. Norbert Tietz, 13th November 1926–23rd May 2018
  7. Reviews
  8. Procalcitonin guidance in patients with lower respiratory tract infections: a systematic review and meta-analysis
  9. Telomere biology and age-related diseases
  10. Opinion Paper
  11. Procalcitonin-guided antibiotic therapy: an expert consensus
  12. Genetics and Molecular Diagnostics
  13. mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population
  14. General Clinical Chemistry and Laboratory Medicine
  15. External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact
  16. Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes
  17. Observational studies on macroprolactin in a routine clinical laboratory
  18. Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results
  19. Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility
  20. Hematology and Coagulation
  21. Analytical performance of an automated volumetric flow cytometer for quantitation of T, B and natural killer lymphocytes
  22. Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity
  23. Reference Values and Biological Variations
  24. Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women
  25. Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects
  26. Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents
  27. Cancer Diagnostics
  28. Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations
  29. Cardiovascular Diseases
  30. Clinical performance of a new point-of-care cardiac troponin I test
  31. Diabetes
  32. Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early β-cell function impairment
  33. Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods
  34. Infectious Diseases
  35. Serum procalcitonin concentration within 2 days postoperatively accurately predicts outcome after liver resection
  36. Predictive value of serum gelsolin and Gc globulin in sepsis – a pilot study
  37. Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis
  38. Letter to the Editor
  39. Glucose and total protein: unacceptable interference on Jaffe creatinine assays in patients
  40. Interference of glucose and total protein on Jaffe-based creatinine methods: mind the covolume
  41. Interference of glucose and total protein on Jaffe based creatinine methods: mind the covolume – reply
  42. Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia
  43. Paraprotein interference in the diagnosis of hepatitis C infection
  44. Timeo apis mellifera and dona ferens: bee sting-induced Kounis syndrome
  45. Bacterial contamination of reusable venipuncture tourniquets in tertiary-care hospital
  46. Detection of EDTA-induced pseudo-leukopenia using automated hematology analyzer with VCS technology
  47. Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis
  48. Thromboelastometry reveals similar hemostatic properties of purified fibrinogen and a mixture of purified cryoprecipitate protein components
  49. Bicarbonate interference on cobas 6000 c501 chloride ion-selective electrodes
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 17.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2017-0882/html
Scroll to top button