Role of Transcription Factor 7 like 2 and Silent Information Regulator 1 Genes in the Development of Cardiovascular Complications in a Group of Egyptian Patients with Chronic Kidney Disease

Doaa Mamdouh; Hanan Shawky; Nihal Moustafa El-Assaly; Samia El-Shishtawy; Nevine  Sherif; Amna  Metwaly; Asmaa Mohamed Fteah

doi:10.3889/oamjms.2022.8107

Authors

Doaa Mamdouh Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt https://orcid.org/0000-0003-0886-3866
Hanan Shawky Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt
Nihal Moustafa El-Assaly Department of Clinical Chemistry
Samia El-Shishtawy Department of Nephrology, Theodor Bilharz Research Institute, Giza, Egypt
Nevine Sherif Department of Nephrology, Theodor Bilharz Research Institute, Giza, Egypt
Amna Metwaly Intensive Care Unit, Theodor Bilharz Research Institute, Giza, Egypt
Asmaa Mohamed Fteah Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt

DOI:

https://doi.org/10.3889/oamjms.2022.8107

Keywords:

Chronic kidney disease, Cardiovascular diseases, Polymerase chain reaction, Single nucleotide polymorphisms, Silent information regulator 1, Transcription factor 7-like 2

Abstract

BACKGROUND: Sirtuins silent information regulator 1 (SIRT) is histone deacetylases that act as antioxidants and involved in the pathogenesis of cardiovascular diseases (CVD) which are the major complications of chronic kidney disease (CKD). Transcription factor 7-like 2 (TCF7L2) genetic polymorphisms could contribute to the risk of CVD as TCF7L2 proteins regulate vascular remodeling.

AIM: We tried to demonstrate the role of genetic polymorphisms: rs7069102 and rs10823108 in SIRT1 gene and rs7903146 in TCF7L2 gene in the development of CVD in CKD Egyptian patients.

METHODS: This study included 120 CKD patients (60 with CVD and 60 without CVD) and 60 age and sex-matched healthy subjects as a control group. Routine laboratory investigations were performed and genotyping for candidate single nucleotide polymorphisms was done by Taqman-real-time polymerase chain reaction.

RESULTS: The frequency of the C allele of rs7069102 was significantly higher in CKD patients with CVD as compared to the normal control group (p < 0.001) and as compared to CKD patients without CVD (p < 0.001). Percentages of AG and GG genotypes of rs10823108 were significantly higher in CKD patients with CVD as compared to the normal control group (p = 0.002, 0.035, respectively). The frequency of the T allele of rs7903146 was significantly higher in CKD patients with CVD as compared to the normal control group (p < 0.001).

CONCLUSION: We found that C allele of rs7069102, GG and AG genotypes of rs10823108 in the SIRT1 gene and T allele of rs7903146 in TCF7L2 gene have a potential role in the pathogenesis and the risk of CVD development in CKD Egyptian patients.

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References

Provenzano M, Coppolino G, Nicola LD, Serra R, Garofalo C, Andreucci M, et al. Unraveling cardiovascular risk in renal patients: A new take on old tale. Front Cell Dev Biol. 2019;7:314. https://doi.org/10.3389/fcell.2019.00314 PMid:31850348 DOI: https://doi.org/10.3389/fcell.2019.00314

Xie Y, Bowe B, Mokdad AH, Xian H, Yan Y, Li T, et al. Analysis of the global burden of disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int. 2018;94(3):567-81. https://doi.org/10.1016/j.kint.2018.04.011 PMid:30078514 DOI: https://doi.org/10.1016/j.kint.2018.04.011

Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389(10075):1238-52. https://doi.org/10.1016/S0140-6736(16)32064-5 PMid:27887750 DOI: https://doi.org/10.1016/S0140-6736(16)32064-5

Cañadas-Garre M, Anderson K, Mcgoldrick J, Maxwell A, Mcknight A. Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease. J Proteomics. 2019;193:93-122. https://doi.org/10.1016/j.jprot.2018.09.020 PMid:30292816 DOI: https://doi.org/10.1016/j.jprot.2018.09.020

Xue P, Cao H, Ma Z, Zhou Y, Wang N. Transcription factor 7-like 2 gene-smoking interaction on the risk of diabetic nephropathy in Chinese Han population. Genes Environ. 2021;43(1):26. https://doi.org/10.1186/s41021-021-00194-2 PMid:34193317 DOI: https://doi.org/10.1186/s41021-021-00194-2

Kaur N, Bhatti GK, Kaur S, Bhadada SK, Singh S, Bhatti JS. Transcription factor 7-like 2 genes, rs12255372 (G/T) variant and susceptibility to Type 2 diabetes mellitus in North Indians. Gene Rep. 2020;19:100595. DOI: https://doi.org/10.1016/j.genrep.2020.100595

Morigi M, Perico L, Benigni A. Sirtuins in renal health and disease. J Am Soc Nephrol. 2018;29(7):1799-809. https://doi.org/10.1681/ASN.2017111218 PMid:29712732 DOI: https://doi.org/10.1681/ASN.2017111218

Sosnowska B, Mazidi M, Penson P, Gluba-Brzózka A, Rysz J, Banach M. The sirtuin family members SIRT1, SIRT3 and SIRT6: Their role in vascular biology and atherogenesis. Atherosclerosis. 2017;265:275-82. https://doi.org/10.1016/j.atherosclerosis.2017.08.027 PMid:28870631 DOI: https://doi.org/10.1016/j.atherosclerosis.2017.08.027

Xiong H, Chen S, Lai L, Yang H, Xu Y, Pang J, et al. Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis. Neurobiol Aging. 2019;79:30-42. https://doi.org/10.1016/j.neurobiolaging.2019.03.013. PMid:31026620 DOI: https://doi.org/10.1016/j.neurobiolaging.2019.03.013

Chan SH, Hung CH, Shih JY, Chu PM, Cheng YH, Lin HC, et al. SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease. Redox Biol. 2017;13:301-9. https://doi.org/10.1016/j.redox.2017.05.027 PMid:28601780 DOI: https://doi.org/10.1016/j.redox.2017.05.027

Kristensen VN, Kelefiotis D, Kristensen T, Børresen-Dale AL. High-throughput methods for detection of genetic variation. Biotechniques. 2001;30(2):318-32, 324, 326. https://doi.org/10.2144/01302tt01 PMid:11233601 DOI: https://doi.org/10.2144/01302tt01

Chan YH. Biostatistics 102: Quantitative data-parametric and non-parametric tests. Singapore Med J. 2003;44(8):391-6.

Chan YH. Biostatistics 103: Qualitative data-tests of Independence. Singapore Med J. 2003;44(10):498-503. PMid:15024452

Yamac AH, Uysal O, Ismailoglu Z, Ertürk M, Celikten M, Bacaksiz A, et al. Premature myocardial infarction: Genetic variations in SIRT1 affect disease susceptibility. Cardiol Res Pract. 2019;2019:8921806. https://doi.org/10.1155/2019/8921806 PMid:31143479 DOI: https://doi.org/10.1155/2019/8921806

Spoto B, Ntounousi E, Testa A, Liakopoulos V, D’Arrigo G, Tripepi G, et al. The sirtuin1 gene associates with left ventricular myocardial hypertrophy and remodeling in two chronic kidney disease cohorts. J Hypertens. 2018;36(8):1705-11. https://doi.org/10.1097/HJH.0000000000001746 PMid:29702498 DOI: https://doi.org/10.1097/HJH.0000000000001746

Yue XG, Yang ZG, Zhang Y, Qin GJ, Liu F. Correlations between SIRT1 gene polymorphisms and diabetic kidney disease. R Soc Open Sci. 2018;5(6):171871. https://doi.org/10.1098/rsos.171871 PMid:30110438 DOI: https://doi.org/10.1098/rsos.171871

Letonja J, Završnik M, Makuc J, Šeruga M, Peterlin A, Cilenšek I, et al. Sirtuin 1 rs7069102 polymorphism is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. Bosnian J Basic Med Sci. 2021;21(5):642-6. https://doi.org/10.17305/bjbms.2020.5368 PMid:33577446 DOI: https://doi.org/10.17305/bjbms.2020.5368

Kurylowicz A. In search of new therapeutic targets in obesity treatment: Sirtuins. Int J Mol Sci. 2016;17(4):572. https://doi.org/10.3390/ijms17040572 PMid:27104517 DOI: https://doi.org/10.3390/ijms17040572

Zhou C, Shi Z, Ouyang N, Ruan X. Hyperphosphatemia and cardiovascular disease. Front Cell Dev Biol. 2021;9:644363. https://doi.org/10.3389/fcell.2021.644363 PMid:33748139 DOI: https://doi.org/10.3389/fcell.2021.644363

Buraczynska M, Zukowski P, Ksiazek P, Kuczmaszewska A, Janicka J, Zaluska W. Transcription factor 7-like 2 (TCF7L2) gene polymorphism and clinical phenotype in end-stage renal disease patients. Mol Biol Rep. 2014;41(6):4063-8. https://doi.org/10.1007/s11033-014-3275-6 PMid:24574000 DOI: https://doi.org/10.1007/s11033-014-3275-6

Kulkarni S, Lenin M, Ramesh R, Delphine SW, Velu K. Evaluation of single-nucleotide polymorphisms of transcription factor 7-like 2 and ATP2B1 genes as cardiovascular risk predictors in chronic kidney disease. Int J Appl Basic Med Res. 2019;9(4):221-5. https://doi.org/10.4103/ijabmr.IJABMR_92_19 PMid:31681547 DOI: https://doi.org/10.4103/ijabmr.IJABMR_92_19

Zhuang Y, Niu F, Liu D, Sun J, Zhang X, Zhang J, et al. Associations of TCF7L2 gene polymorphisms with the risk of diabetic nephropathy. Medicine (Baltimore). 2018;97(40):e8388. https://doi.org/10.1097/MD.0000000000008388 PMid:30290587 DOI: https://doi.org/10.1097/MD.0000000000008388