ANALYSIS OF THE ASSOCIATION OF RS4977574-POLYMORPHIC VARIANTS OF THE ANRIL GENE WITH THE DEVELOPMENT OF ACUTE CORONARY SYNDROME IN INDIVIDUALS WITH DIFFERENT BODY MASS INDEX IN THE UKRAINIAN POPULATION

Keywords: gene polymorphism, ANRIL, rs4977574, acute coronary syndrome

Abstract

The objective was to analyze the association of rs4977574-polymorphic variants of the ANRIL gene with the development of acute coronary syndrome in individuals with different body mass index.

Materials and methods. The venous blood of 429 people (234 patients with acute coronary syndrome and 195 people in the control group) was used for the study. Genotyping of patients by rs4977574-polymorphic variants of the ANRIL gene was performed by real-time polymerase chain reaction (Real-time PCR) in the presence of TaqMan assay C_31720978_30. Statistical analysis of the results of the study was performed using SPSS software (version 17.0).

Results. The distribution of genotypes according to SNP rs4977574 of the ANRIL gene in the group of patients with ACS and the control group among individuals with BMI < 25 kg/m2 does not differ. Among patients with BMI 25 kg/m2 the genotype distribution of the rs4977574-polymorphic variant of the ANRIL gene was statistically significant (р = 0.035). In the group of patients with BMI > 25 kg/m2 according to recessive (Pobserv = 0.014; ORobserv = 1.876, 95 % СІ = 1.137–3.095) and additive (Рobserv = 0.014; ORobserv = 2.118, 95% СІ = 1.166–3.849) models of inheritance before making adjustment, people with G/G genotype had a double risk of acquiring ACS than carriers of the dominant allele. After the adjustment, corresponding models of inheritance had the same risk rate – for recessive model (Рadjust = 0.013; ORadjust = 1.951, 95% СІ = 1.149–3.313) and additive model (Рadjust = 0.026; ORadjust = 2.039, 95 % СІ = 1.087–3.826).

Conclusions. Individuals with BMI > 25 kg/m2, which were carriers of G/G genotype had a 2 times higher risk to acquire ACS than the individuals with the dominant allele.

Prospects for further research. Further research will be aimed at studying the impact of ANRIL polymorphism upon the risk of ACS development depending on other risk factors.

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References

ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012 Sep 6;489(7414):57-74. doi: 10.1038/nature11247. PMID: 22955616; PMCID: PMC3439153.

Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860-921. doi: 10.1038/35057062. Erratum in: Nature 2001 Aug 2;412(6846):565. Erratum in: Nature 2001 Jun 7;411(6838):720. Szustakowki, J [corrected to Szustakowski, J]. PMID: 11237011.

Mattick JS. Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep. 2001 Nov;2(11):986-91. doi: 10.1093/embo-reports/kve230. PMID: 11713189; PMCID: PMC1084129.

Liu C, Bai B, Skogerbø G, Cai L, Deng W, Zhang Y, et al. NONCODE: an integrated knowledge database of non-coding RNAs. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D112-5. doi: 10.1093/nar/gki041. PMID: 15608158; PMCID: PMC539995.

Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al. RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group). The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. doi: 10.1126/science.1112014. Erratum in: Science. 2006 Mar 24;311(5768):1713. PMID: 16141072.

Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013 Mar;20(3):300-7. doi: 10.1038/nsmb.2480. PMID: 23463315.

Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011 Sep 16;43(6):904-14. doi: 10.1016/j.molcel.2011.08.018. PMID: 21925379; PMCID: PMC3199020.

Amodio N, Raimondi L, Juli G, Stamato MA, Caracciolo D, Tagliaferri P, et al. MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches. J Hematol Oncol. 2018 May 8;11(1):63. doi: 10.1186/s13045-018-0606-4. PMID: 29739426; PMCID: PMC5941496.

Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol. 2010 Jan;220(2):126-39. doi: 10.1002/path.2638. PMID: 19882673.

Akhade VS, Pal D, Kanduri C. Long Noncoding RNA: Genome Organization and Mechanism of Action. Adv Exp Med Biol. 2017;1008:47-74. doi: 10.1007/978-981-10-5203-3_2. PMID: 28815536.

Congrains A, Kamide K, Ohishi M, Rakugi H. ANRIL: molecular mechanisms and implications in human health. Int J Mol Sci. 2013 Jan 10;14(1):1278-92. doi: 10.3390/ijms14011278. PMID: 23306151; PMCID: PMC3565320.

Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014 Dec 18;159(7):1665-80. doi: 10.1016/j.cell.2014.11.021. Epub 2014 Dec 11. Erratum in: Cell. 2015 Jul 30;162(3):687-8. PMID: 25497547; PMCID: PMC5635824.

Huang X, Zhang W, Shao Z. Association between long non-coding RNA polymorphisms and cancer risk: a meta-analysis. Biosci Rep. 2018 Jul 31;38(4):BSR20180365. doi: 10.1042/BSR20180365. PMID: 29802154; PMCID: PMC6066654.

Qiao L, Wen XY, Dou KF, et al. Correlation study between CDKN2B-AS1 gene polymorphism and female premature coronary artery disease occurrence. Chinese Circ J. 2017;32:1154-1157. doi: 10.3969/j.issn.1000-3614.2017.12.003

Kong Y, Sharma RB, Nwosu BU, Alonso LC. Islet biology, the CDKN2A/B locus and type 2 diabetes risk. Diabetologia. 2016 Aug;59(8):1579-93. doi: 10.1007/s00125-016-3967-7. Epub 2016 May 7. PMID: 27155872; PMCID: PMC4930689.

Rezazadeh M, Gharesouran J, Moradi M, Noroozi R, Omrani MD, Taheri M, et al. Association Study of ANRIL Genetic Variants and Multiple Sclerosis. J Mol Neurosci. 2018 May;65(1):54-59. doi: 10.1007/s12031-018-1069-3. Epub 2018 Apr 30. PMID: 29713948.

Huang Y, Ye H, Hong Q, Xu X, Jiang D, Xu L, et al. Association of CDKN2BAS polymorphism rs4977574 with coronary heart disease: a case-control study and a meta-analysis. Int J Mol Sci. 2014 Sep 29;15(10):17478-92. doi: 10.3390/ijms151017478. PMID: 25268619; PMCID: PMC4227174.

Wang Y, Wang L, Liu X, Zhang Y, Yu L, Zhang F, et al. Genetic variants associated with myocardial infarction and the risk factors in Chinese population. PLoS One. 2014 Jan 27;9(1):e86332. doi: 10.1371/journal.pone.0086332. PMID: 24475106; PMCID: PMC3903528.

Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011 Mar 6;43(4):333-8. doi: 10.1038/ng.784. PMID: 21378990; PMCID: PMC3119261.

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267-315. doi: 10.1093/eurheartj/ehv320. Epub 2015 Aug 29. PMID: 26320110.

Gil J, Peters G. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol. 2006 Sep;7(9):667-77. doi: 10.1038/nrm1987. PMID: 16921403.

Congrains A, Kamide K, Katsuya T, Yasuda O, Oguro R, Yamamoto K, et al. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. Biochem Biophys Res Commun. 2012 Mar 23;419(4):612-6. doi: 10.1016/j.bbrc.2012.02.050. Epub 2012 Feb 20. PMID: 22382030.

Ibdah RK, Al-Eitan LN, Alrabadi NN, Almasri AY, Alnaamneh AH, Khasawneh RH, et al. Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity. Int J Gen Med. 2021 Jan 14;14:103-118. doi: 10.2147/IJGM.S287238. PMID: 33488114; PMCID: PMC7814275.

Li YY, Wang H, Zhang YY. CDKN2B-AS1 gene rs4977574 A/G polymorphism and coronary heart disease: A meta-analysis of 40,979 subjects. J Cell Mol Med. 2021 Sep;25(18):8877-8889. doi: 10.1111/jcmm.16849. Epub 2021 Aug 21. PMID: 34418317; PMCID: PMC8435436.

Huang Y, Ye H, Hong Q, Xu X, Jiang D, Xu L et al. Association of CDKN2BAS polymorphism rs4977574 with coronary heart disease: a case-control study and a meta-analysis. Int J Mol Sci. 2014 Sep 29;15(10):17478-92. doi: 10.3390/ijms151017478. PMID: 25268619; PMCID: PMC4227174.

Cao XL, Yin RX, Huang F, Wu JZ, Chen WX. Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population. Int J Mol Sci. 2016 Apr 18;17(4):586. doi: 10.3390/ijms17040586. PMID: 27096864; PMCID: PMC4849041.

Published
2022-06-30
How to Cite
1.
Polina V. Kniazkova, Viktoriia Yu. Harbuzova. ANALYSIS OF THE ASSOCIATION OF RS4977574-POLYMORPHIC VARIANTS OF THE ANRIL GENE WITH THE DEVELOPMENT OF ACUTE CORONARY SYNDROME IN INDIVIDUALS WITH DIFFERENT BODY MASS INDEX IN THE UKRAINIAN POPULATION. East Ukr Med J [Internet]. 2022Jun.30 [cited 2024Mar.29];10(2):147-54. Available from: https://eumj.med.sumdu.edu.ua/index.php/journal/article/view/250