Evaluation of metabolic disorders and aging rates depending on SIRT1 polymorphism in patients with arterial hypertension and subclinical hypothyroidism

A.O. Radchenko; O.V.  Kolesnikova

doi:10.26641/2307-0404.2022.4.271180

Authors

A.O. Radchenko L.T. Mala Therapy National Institute of the National Academy of Medical Sciences of Ukraine, L. Maloi ave., 2а, Kharkiv, 61039, Ukraine https://orcid.org/0000-0002-9687-8218
O.V. Kolesnikova L.T. Mala Therapy National Institute of the National Academy of Medical Sciences of Ukraine, L. Maloi ave., 2а, Kharkiv, 61039, Ukraine https://orcid.org/0000-0001-5606-6621

DOI:

https://doi.org/10.26641/2307-0404.2022.4.271180

Keywords:

arterial hypertension, subclinical hypothyroidism, aging, metabolic diseases, SIRT1

Abstract

There is an increase in the frequency and severity of metabolic disorders in patients with arterial hypertension (AH) in combination with subclinical hypothyroidism (SH), that is accompanied by accelerated aging rates, but the research findings on the aging rates in this category of patients are extremely few in number. Therefore, the aim of our study was to assess metabolic disorders and the aging rates depending on the SIRT1 rs7069102 polymorphism in patients with AH and SH. A total of 132 patients with a median age of 47.6 years were included in the study and divided into 3 groups: a control group (n=30), a group of patients with AH without SH (n=49) and patients with AH in combination with SH (n=53). Anthropometric parameters, biochemical parameters, pro-inflammatory and oxidative states were evaluated in all patients. The aging rates were assessed using two different methods. The frequencies of SIRT1 rs7069102 genotypes carriers in the study sample of patients were 8% for the CC genotype, 51% for the CG genotype and 41% for the GG genotype. There was a significant difference in the incidence of CC homozygosity and carriers of the G allele between groups of patients with AH depending on the SH presence (p<0.001). We showed that carriers of the G allele and GG genotype of the SIRT1 gene (rs7069102) polymorphic marker with AH and SH had significantly higher (p<0.05) insulin resistance, higher levels of low-density lipoprotein cholesterol, alkaline phosphatase, C-reactive protein and lower glomerular filtration rate, which negatively affected the aging processes in this category of patients. In addition, patients with AH had a marked effect of carrying the G allele on the lipid profile and biological age of patients. Therefore, timely detection of a polymorphic variant of the SIRT1 gene may be effective in premature aging prevention in patients with AH and SH.

References

Kolesnikova OV, Radchenko AO. [Modern view on the mechanisms of oxidative stress and its biomarkers in a larger number of non-communicable diseases]. Ukrain. Therap. J. 2020;1:51-61. Ukrainian.

Delitala AP, Scuteri A, Maioli M, Mangatia P, Vilardi L, Erre GL. Subclinical hypothyroidism and cardiovascular risk factors. Minerva medica. 2019 Nov 11;110(6):530-45. doi: https://doi.org/10.23736/S0026-4806.19.06292-X

Kilic U, Gok O, Bacaksiz A, Izmirli M, Elibol-Can B, Uysal O. SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases. PloS one. 2014 Feb 28;9(2):e90428. doi: https://doi.org/10.1371/journal.pone.0090428

Peeters AV, Beckers S, Verrijken A, Mertens I, Roevens P, et al. Association of SIRT1 gene variation with visceral obesity. Human genetics. 2008 Nov 1;124(4):431. doi: https://doi.org/10.1371/journal.pone.0115339

Alamdari DH, Paletas K, Pegiou T, Sarigianni M, Befani C, Koliakos G. A novel assay for the evaluation of the prooxidant–antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients. Clinical biochemistry. 2007 Feb 1;40(3-4):248-54. doi: https://doi.org/10.1016/j.clinbiochem.2006.10.017

Voitenko VP, Tokar AV, Rudaia ES. [Method of determining biological age]. Voprosy gerontologii. 1989;11:9. Russian.

Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018 Apr;10(4):573. doi: https://doi.org/10.18632/aging.101414

Antomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv: Medinform; 2017. Russian.

Habieb MS, Abdel-Aziz WF, Ismail AH, Sallam KM, El-Shafie MK. Sirtuin1 and Sirtuin3 gene polymorphisms and acute myocardial infarction susceptibility. Meta Gene. 2021 Dec 1;30:100965. doi: https://doi.org/10.1016/j.mgene.2021.100965

Shimoyama Y, Mitsuda Y, Tsuruta Y, Suzuki K, Hamajima N, Niwa T. SIRTUIN 1 gene polymorphisms are associated with cholesterol metabolism and coronary artery calcification in Japanese hemodialysis patients. Journal of Renal Nutrition. 2012 Jan 1;22(1):114-9. doi: https://doi.org/10.1053/j.jrn.2011.10.025

Kilic U, Gok O, Erenberk U, Dundaroz MR, Torun E, Kucukardali Y, et al. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PloS one. 2015 Mar 18;10(3):e0117954. doi: https://doi.org/10.1371/journal.pone.0117954

Letonja J, Završnik M, Makuc J, Šeruga M, Peterlin A, Cilenšek I, Petrovič D. Sirtuin 1 rs7069102 polymorphism is associated with diabetic nephropathy in patients with type 2 diabetes mellitus. Bosnian Journal of Basic Medical Sciences. 2021 Oct;21(5):642. doi: https://doi.org/10.17305/bjbms.2020.5368

Ji JS, Liu L, Shu C, Yan LL, Zeng Y. Sex Difference and Interaction of SIRT1 and FOXO3 Candidate Longevity Genes on Life Expectancy: A 10-Year Prospective Longitudinal Cohort Study. The Journals of Gerontology: Series A. 2021 Dec 20;2021:glab378. doi: https://doi.org/10.1093/gerona/glab378