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Analysis of Association of Angiotensin II Type 1 Receptor Gene A1166C Gene Polymorphism with Essential Hypertension

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Abstract

The A/C transversion at 1166 of the angiotensin II Type 1 Receptor (AT1R) gene per se does not characterize any functional diversity but has been associated with expression of the AT1R, consequently molecular variants of the gene may modulate the possible risk of essential hypertension. The present study was performed to determine the genotypic frequency of the A1166C polymorphism of the AT1R gene in essential hypertensive patients with the aim to assess the effect of variants of this polymorphism in hypertension. AT1R gene amplification was performed by PCR and A1166C polymorphism was determined by enzyme digestion methodologies in 224 consecutively enrolled essential hypertensive patients and 257 controls. Suitable descriptive statistics was used for different variables. Results revealed that genotype and allele distribution of the A1166C variant differed significantly in hypertensives and normotensives. Allele frequency at the A1166C position was 61%A and 39%C for control and 52%A and 48%C for patients. Observed frequencies were compatible with HWE expected frequencies in cases as well as in controls. rs5186 was found to be associated with hypertension (95% CI 1.1453–2.7932, p: 0.0106). The difference remained statistically significant after the multivariate adjustment (p < 0.05), with C/C variant conferring a risk of 1.74-fold of essential hypertension. This association was confirmed by inter-genotypic variations in the mean systolic and diastolic blood pressure in patients. In conclusion, genetic variation at the AT1R gene influences the risk of hypertension stratification and might serve as a predictive marker for the susceptibility to hypertension among affected families.

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References

  1. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104:545–56.

    Article  CAS  PubMed  Google Scholar 

  2. Butler MG. Genetics of hypertension: current status. J Med Liban. 2010;58:175–8.

    PubMed  PubMed Central  Google Scholar 

  3. Navar LG, Kobori H, Prieto MC, Gonzalez-Villalobos RA. Intratubular renin-angiotensin system in hypertension. Hypertension. 2011;57:355–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33:2088–97.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jiang ZN, Zhao WS, Yu F, Xu G. Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Chin Med J. 2001;114:1249–51.

    CAS  PubMed  Google Scholar 

  6. Chiu AT, Herblin WF, McCall DE, Ardecky RJ, Carini DJ, Duncia JV, et al. Identification of angioensin II receptor subtypes. Biochem Biophys Res Commun. 1989;165:196–203.

    Article  CAS  PubMed  Google Scholar 

  7. Katovich MJ, Gelband CH, Reaves P, Wang HW, Raizada MK. Reversal of hypertension by angiotensin II type 1 receptor antisense gene therapy in the adult SHR. Am J Physiol. 1999;277:H1260–4.

    CAS  PubMed  Google Scholar 

  8. Bonnardeaux A, Davies E, Jeunemaitre X, Féry I, Charru A, Clauser E, et al. Angiotensın II Type 1 receptor gene polymorphism in human essential hypertension. Hypertension. 1994;24:63–9.

    Article  CAS  PubMed  Google Scholar 

  9. Wang JL, Xue Li, Hao PP, Feng Xu, Chen YG, Zhang Y. Angiotensin II type 1 receptor gene A1166C polymorphism and essential hypertension in Chinese: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2010;11:127–35

    Article  CAS  PubMed  Google Scholar 

  10. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289:2560–72.

    Article  CAS  PubMed  Google Scholar 

  11. Raizada MK, Sumners C, Lu D. Angiotensin II type 1 receptor mRNA levels in the brains of normotensive and spontaneously hypertensive rats. J Neurochem. 1993;60:1949–52.

    Article  CAS  PubMed  Google Scholar 

  12. Reja V, Goodchild AK, Phillips JK, Pilowsky PM. Upregulation of angiotensin AT1 receptor and intracellular kinase gene expression in hypertensive rats. Clin Exp Pharmacol Physiol. 2006;33:690–5.

    Article  CAS  PubMed  Google Scholar 

  13. Chandra S, Narang R, Sreenivas V, Bhatia J, Saluja D, Srivastava K. Association of angiotensin II type 1 receptor (A1166C) gene polymorphism and its increased expression in essential hypertension: a case-control study. PLoS ONE. 2014;9(7):e101502.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ceolotto G, Papparella I, Bortoluzzi A, Strapazzon G, Ragazzo F, Bratti P, et al. Interplay between miR-155, AT1R A1166C polymorphism, and AT1R expression in young untreated hypertensives. Am J Hypertens. 2011;24:241–6.

    Article  CAS  PubMed  Google Scholar 

  15. Brugts JJ, Isaacs A, de Maat MP, Boersma E, van Duijn CM, Akkerhuis KM, et al. A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals. J Hypertens. 2011;29:509–19.

    Article  CAS  PubMed  Google Scholar 

  16. Spiering W, Kroon AA, Fuss-Lejeune MM, Daemen MJ, De Leeuw PW. Angiotensin II sensitivity is associated with the angiotensin II type 1 receptor A(1166)C polymorphism in essential hypertensives on a high sodium diet. Hypertension. 2000;36:411–6.

    Article  CAS  PubMed  Google Scholar 

  17. Bayramoglu A, Kurt H, Gunes HV, Ata N, Birdane A, Dikmen M, et al. Angiotensin II type 1 receptor (AT1) gene A1166C is associated with the risk of hypertension. Genet Test Mol Biomark. 2015;19:14–7.

    Article  CAS  Google Scholar 

  18. Patnaik M, Pati P, Swain SN, Mohapatra MK, Dwibedi B, Kar SK, Ranjit M. Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha. India J Genet. 2014;93:799–808.

    Article  CAS  PubMed  Google Scholar 

  19. Chung WK, Deng L, Carroll JS, Mallory N, Diamond B, Rosenzweig EB, et al. Polymorphism in the angiotensin II Type 1 receptor (AGTR1) is associated with age at diagnosis in pulmonary arterial hypertension. J Heart Lung Transplant. 2009;28:373–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Niu W, Qi Y. Association of the angiotensin II type I receptor gene +1166 A>C polymorphism with hypertension risk: evidence from a meta-analysis of 16474 subjects. Hypertens Res. 2010;33:1137–43.

    Article  CAS  PubMed  Google Scholar 

  21. Shahin DS, Irshaid YM, Saleh AA. The A(1166)C26 polymorphism of the AGTR1 gene is associated with an early onset of hypertension and high waist circumference in Jordanian males attending the Jordan University Hospital. Clin Exp Hypertens. 2014;36:333–9.

    Article  CAS  PubMed  Google Scholar 

  22. Kooffreh ME, Anumudu CI, Duke R, Okpako EC, Kumar PL. Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in Calabar and Uyo cities, Nigeria. Indian J Hum Genet. 2013;19:213–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jiang X, Sheng H, Li J, Xun P, Cheng Y, Huang J, Xiao H, Zhan Y. Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study. J Hum Hypertens. 2009;23:176–81.

    Article  CAS  PubMed  Google Scholar 

  24. Sugimoto K, Katsuya T, Ohkubo T, Hozawa A, Yamamoto K, Matsuo A, et al. Association between angiotensin II type 1 receptor gene polymorphism and essential hypertension: the Ohasama study. Hypertens Res. 2004;27:551–6.

    Article  CAS  PubMed  Google Scholar 

  25. Van Geel PP, Pinto YM, Voors AA, Buikema H, Oosterga M, Crijns HJ, et al. Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries. Hypertension. 2000;35:717–21.

    Article  PubMed  Google Scholar 

  26. Thekkumkara TJ, Linas SL. Evidence for involvement of 3′-untranslated region in determining angiotensin II receptor coupling specificity to G-protein. Biochem J. 2003;370:631–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Atkinson TJ, Halfon MS. Regulation of gene expression in the genomic context. Comput Struct Biotechnol J. 2014;9:e201401001.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS, et al. Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet. 2007;81:405–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang J, Chuang K, Ahluwalia M, Patel S, Umblas N, Mirel D, et al. High-throughput SNP genotyping by single-tube PCR with Tm-shift primers. Biotechniques. 2005;39:885–93.

    Article  CAS  PubMed  Google Scholar 

  30. Hattersley AT, McCarthy MI. What makes a good genetic association study? Lancet. 2005;366:1315–23.

    Article  PubMed  Google Scholar 

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Correspondence to Deepak N. Parchwani.

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Parchwani, D.N., Patel, D.D., Rawtani, J. et al. Analysis of Association of Angiotensin II Type 1 Receptor Gene A1166C Gene Polymorphism with Essential Hypertension. Ind J Clin Biochem 33, 53–60 (2018). https://doi.org/10.1007/s12291-017-0644-7

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  • DOI: https://doi.org/10.1007/s12291-017-0644-7

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