Association between KLOTHO Gene G395A Polymorphism and Carotid Artery Calcification in regular Hemodialysis Patients

Authors

  • Herwindo Ahmad Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia
  • Riri Andri Muzasti Division of Nephrology-Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia
  • Syafrizal Nasution Division of Nephrology-Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2020.3790

Keywords:

Chronic kidney disease, KLOTHO, Polymorphism, Vascular classification

Abstract

BACKGROUND: The vascular calcification process in chronic kidney disease (CKD) is a complication caused by mineral and bone abnormalities and becomes the risk of cardiovascular disease and mortality in CKD patients. KLOTHO is an inhibitor of calcification and its expression has been observed to decrease in CKD patients. The KLOTHO gene G395A polymorphism is a genetic variation that is common in Asian populations and is associated with vascular dysfunction in hemodialysis patients.

OBJECTIVE: The objective of the study was to determine the association between the KLOTHO gene G395A polymorphism and carotid artery calcification in regular hemodialysis patients.

METHODS: This study was an analytical study with a cross-sectional design and was carried out at Rasyida Kidney Hospital Medan. Venous blood sample was taken from the patients who met the inclusion criteria for examination of the KLOTHO gene -395 polymorphism and carotid ultrasonography was assessed to evaluate the thickness of the tunica media-intima as a marker of vascular calcification.

RESULTS: The majority of the study subjects were men, as many as 35 patients (50.7%). From the results of the KLOTHO gene -395 polymorphism, it was found that the majority of subjects had GG genotypes as many as 36 people (52.2%) followed by GA genotypes as many as 30 people (43,5%) and AA genotypes as many as 3 (4,3%). There was a statistically significant of the association between KLOTHO gene -395 polymorphism and the incidence of carotid artery calcification (p = 0,015).

CONCLUSION: There was an association between the KLOTHO gene G395A polymorphism and carotid artery calcification in regular hemodialysis patients.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Mills KT, Xu Y, Zhang W, Bundy JD, Chen CS, Kelly T, et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int. 2015;88(5):950-7. https://doi.org/10.1038/ki.2015.230 PMid:26221752

Hwang SJ, Tsai JC, Chen HC. Epidemiology, impact and preventive care of chronic kidney disease in Taiwan. Nephrology. 2010;15(Suppl 2):3-9. https://doi. org/10.1111/j.1440-1797.2010.01304.x PMid:20586940

Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, et al. Peripheral vascular calcification in long-haemodialysis patients: Associated factors and survival consequences. Nephrol Dial Transplant. 2008;24(3):948-55. https://doi.org/10.1093/ndt/ gfn571 PMid:18852190

Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM. Exploring the biology of vascular calcification in chronic kidney disease: What’s circulating? Kidney Int. 2008;73(4):384-90. https://doi. org/10.1038/sj.ki.5002696 PMid:18046319

Yamada S, Giachelli CM. Vascular calcification in CKD-MBD: Roles for phosphate, FGF23. Bone. 2017;100:87-93. https://doi. org/10.1016/j.bone.2016.11.012 PMid:27847254

Ko GJ, Lee Ym, Lee EA, Lee JE, Bae SY, Park SW, et al. The association of klotho gene polymorphism with the mortality of patients on maintenance dialysis. Clin Nephrol. 2013;80(4):263- 9. https://doi.org/10.1016/j.cca.2009.06.011 PMid:23993164

Sripichai O, Fucharoen S. Genetic polymorphisms and implications for human diseases. J Med Assoc Thai. 2007;90(2):394-8. PMid:17375650

Nazarian A, Hasankhani M, Aghajany-Nasab M, Monfared A. Association between klotho gene polymorphism and markers of bone metabolism in patients receiving maintenance hemodialysis in Iran. Iran J Kidney Dis. 2017;11(6):454-60. PMid:29190606

Shimoyama Y, Nishio K, Hamajima N, Niwa T. KLOTHO gene polymorphisms G-395a and C1818t are associated with lipid and glucose metabolism, bone mineral density and systolic blood pressure in Japanese healthy subjects. Clin Chim Acta. 2009;406(1-2):134-8. PMid:19539617

Bauer M, Caviezel S, Teynor A, Erbel R, Mahabadi AA, Schmidt- Trucksäss A. Carotid intima-media thickness as a biomarker of subclinical atherosclerosis. Swiss Med Wkly. 2012;142:w13705. https://doi.org/10.4414/smw.2012.13705 PMid:23135891

Lebov JF, Valladares E, Peña R, Sanoff SL, Cisneros EC, Colindres RE, et al. A population-based study of prevalence and risk factors of chronic kidney disease in León, Nicaragua. Can J Kidney Health Dis. 2015;2:6. https://doi.org/10.1186/ s40697-015-0041-1 PMid:25926994

Carrero JJ, Hecking M, Chesnaye NC, Jager KJ. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol. 2018;14(3):151-64. https:// doi.org/10.1038/nrneph.2017.181 PMid:29355169

Doublier S, Lupia E, Catanuto P, Periera-Simon S, Xia X, Korach K, et al. Testosterone and 17β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice. Kidney Int. 2011;79(4):404-13. https://doi.org/10.1038/ki.2010.398 PMid:20962747

Maric C, Xu Q, Sandberg K, Hinojosa-Laborde C. Age-related renal disease in female Dahl salt-sensitive rats is attenuated with 17β-estradiol supplementation by modulating nitric oxide synthase expression. Gend Med. 2008;5(2):147-59. https://doi. org/10.1016/j.genm.2008.05.002 PMid:18573482

Goldberg I, Krause I. The role of gender in chronic kidney disease end-stage renal disease among. EMJ. 2016;1(2):58-64.

Indonesian Renal Registry. 10th Report of Indonesian Renal Registry; 2017. Available from: https://www. indonesianrenalregistry.org/data/IRR%202017%20.pdf. [Last accessed on 2019 Apr 22].

Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, et al. Prevalence of chronic kidney disease in China: A cross-sectional survey. Lancet. 2012;379(9818):815-22. https://doi. org/10.1016/s0140-6736(12)60033-6 PMid:22386035

Wang XC, Liu CH, Chen YJ, Wu Y, Yang LS, Liu HM, et al. Clinical and pathological analysis of the kidney in patients with hypertensive nephropathy. Exp Ther Med. 2013;6:1243-6. PMid:24223652

Bernheim J, Benchetrit S. The potential roles of FGF23 and klotho in the prognosis of renal and cardiovascular diseases. Nephrol Dial Transplant. 2011;26:2433-8. https://doi. org/10.1093/ndt/gfr208 PMid:21543658

Ding HY, Ma HX. Significant roles of anti-aging protein KLOTHO and fibroblast growth factor 23 in cardiovascular disease. J Geriatr Cardiol. 2015;12:439-47. PMid:26347327

Torres PU, Prie D, Molina-Bletry V, Beck L, Silve C, Friedlander G. KLOTHO: An Antiaging Protein Involved in Mineral and Vitamin D Metabolism. Kidney Int. 2007;71:730-7. https://doi.org/10.1038/sj.ki.5002163

Lu X, Hu MC. KLOTHO/FGF23 axis in chronic kidney disease and cardiovascular disease. Kidney Dis. 2017;3(1):15-23. https://doi.org/10.1159/000452880 PMid:28785560

Afanas’ev I. Reactive oxygen species and age-related genes p66Shc, sirtuin, FoxO3 and KLOTHO in senescence. Oxid Med Cell Longev. 2010;3(2):77-85. https://doi.org/10.4161/ oxim.3.2.11050 PMid:20716932

Nitta K, Nagano N, Tsuchiya K. Fibroblast growth factor 23/ KLOTHO axis in chronic kidney disease. Nephron Clin Pract. 2014;128(1-2):1-10. https://doi.org/10.1159/000365787 PMid:25402964

Vervloet MG, Adema AY, Larsson TE, Massy ZA. The role of KLOTHO on vascular calcification and endothelial function in chronic kidney disease. Semin Nephrol. 2014;34(6):578-85. https://doi.org/10.1016/j.semnephrol.2014.09.003 PMid:25498377

Kim Y, Jeong SJ, Lee HS, Kim EJ, Song YR, Kim SG, et al. Polymorphism in the promoter region of the KLOTHO gene (G-395A) is associated with early dysfunction in vascular access in hemodialysis patients. Korean J Intern Med. 2008;23(4):201- 7. https://doi.org/10.3904/kjim.2008.23.4.201 PMid:19119257

Zhai C, Tang G, Qian G, Hu H, Gu A, Fang Y, et al. Polymorphism of KLOTHO G-395A and susceptibility of coronary artery disease in East-Asia population: A meta-analysis. Int J Clin Exp Med. 2015;8(2):1582-8. PMid:25932086

Donate-correa J, Mart E, Mart R, Fuentes MM, Mora-Fernández CC, Pérez-Delgado N, et al. Influence of KLOTHO gene polymorphisms on vascular gene expression and its relationship to cardiovascular disease. J Cell Mol Med. 2016;20(1):128-33. https://doi.org/10.1111/jcmm.12710 PMid:26538295

Rhee E, Oh K, Lee W, Kim SY, Jung CH, Kim BJ, et al. The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease. J Metabol. 2006;55:1344-51. https://doi.org/10.1016/j. metabol.2006.05.020 PMid:16979405

Imamura A, Okumura K, Ogawa Y, Murakami R, Torigoe M, Numaguchi Y, et al. klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese. Clin Chim Acta. 2006;371:66- 70. https://doi.org/10.1016/j.cca.2006.02.021 PMid:16579981

Jo S, Kim S, Choi YJ, et al. KLOTHO Gene Polymorphism Is Associated With Coronary Artery Stenosis but Not With Coronary Calcification in a Korean Population. Int Heart J. 2008;1:23-32. https://doi.org/10.1536/ihj.50.23

Jensky NE, Criqui MH, Wright MC, Wassel CL, Brody SA, Allison MA. Blood pressure and vascular calcification. Hypertension AHA. 2010;55:990-7. https://doi.org/10.1161/ hypertensionaha.109.147520

Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events. J Am Cool Cardiol. 2005;46:158-65. https://doi.org/10.1016/j. jacc.2005.02.088

Chen NX, Moe SM. Vascular calcification: Pathophysiology and risk factors. Curr Hypertens Rep. 2012;14(3):228-37. https://doi. org/10.1007/s11906-012-0265-8

Boström KI, Jumabay M, Matveyenko A, Nicholas SB, Yao Y. Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circ Res. 2011;108(4):446-57. https://doi. org/10.1161/circresaha.110.236596 PMid:21193740

Kalra SS, Shanahan CM. Vascular calcification and hypertension: Cause and effect. Ann Med. 2012;44(Suppl 1):S85-92. PMid:22713153

Downloads

Published

2020-05-13

How to Cite

1.
Ahmad H, Muzasti RA, Nasution S. Association between KLOTHO Gene G395A Polymorphism and Carotid Artery Calcification in regular Hemodialysis Patients. Open Access Maced J Med Sci [Internet]. 2020 May 13 [cited 2024 Apr. 25];8(A):208-13. Available from: https://oamjms.eu/index.php/mjms/article/view/3790

Most read articles by the same author(s)