Analysis of the redistribution of rs4977574-polymorphic variants of the ANRIL gen in patients with acute coronary syndrome of different sex

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


Annotation. The aim of the study was to analyze the distribution of rs4977574-polymorphic variants of the ANRIL gene in patients with acute coronary syndrome of different sex. The venous blood of 234 patients with acute coronary syndrome (ACS) and 195 people without cardiac pathology was used for the study. DNA was isolated from whole venous blood using the GeneJET Whole Blood Genomic DNA Purification Mini Kit (ThermoFisher Scientific, USA). rs4977574 ANRIL gene polymorphism was studied by real-time PCR reaction in the presence of TaqMan assay C_31720978_30. Statistical analysis of the study was performed using the SPSS program (version 17.0). A difference was found when comparing the frequencies of genotypes at the polymorphic site rs4977574 of the ANRIL gene in their distribution (p=0,035). According to the results of logistic regression, it was detected that in the recessive (p=0,015) and additive (p=0,012) inheritance models, carriers of the G/G genotype are approximately 2 times more likely to develop ACS than carriers of the A-allele. The reliability of the results was maintained after adjustments for gender, age, B<I, smoking habits, diabetes and stress (p=0,049 for the recessive model; p=0,037 for the additive model). Thus, individuals with the rs4977574 G/G genotype polymorphism of the ANRIL long non-coding RNA gene have a 2 times higher risk of developing ACS than dominant allele carriers. Further research will focus on the association of ANRIL polymorphism with the risk of ACS depending on other risk factors.


[1] AbdulAzeez, S., Al-Nafie, A. N., Al-Shehri, A., Borgio, J. F., Baranova, E. V., Al-Madan, M. S., … & Al-Ali, A. K. (2016). Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population. International journal of molecular sciences, 17(3), 395.

[2] Ahmed, W., Ali, I. S., Riaz, M., Younas, A., Sadeque, A., Niazi, A. K., … & Qamar, R. (2013). Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia. Gene, 515(2), 416-420.

[3] Cánepa, E. T., Scassa, M. E., Ceruti, J. M., Marazita, M. C., Carcagno, A. L., Sirkin, P. F., & Ogara, M. F. (2007). INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB life, 59(7), 419-426.

[4] Gori, F., Specchia, C., Pietri, S., Crociati, L., Barlera, S., Franciosi, M., … Franzosi, M. G. (2010). Common genetic variants on chromosome 9p21 are associated with myocardial infarction and type 2 diabetes in an Italian population. BMC medical genetics, 11, 60.

[5] Huang, Y., Ye, H., Hong, Q., Xu, X., Jiang, D., Xu, L., … & Duan, S. (2014). Association of CDKN2BAS polymorphism rs4977574 with coronary heart disease: a case-control study and a meta-analysis. International journal of molecular sciences, 15(10), 17478-17492.

[6] Kong, Y., Sharma, R. B., Nwosu, B. U., & Alonso, L. C. (2016). Islet biology, the CDKN2A/B locus and type 2 diabetes risk. Diabetologia, 59(8), 1579-1593.

[7] Li, Y‐y., Wang, H., & Zhang, Y‐y. (2021). CDKN2B‐AS gene rs4977574 A/G polymorphism and coronary heart disease: A meta‐analysis of 40,979 subjects. J Cell Mol Med., 25(18), 8877-8889. doi: 10.1111/jcmm.16849

[8] Liu, X., Jiang, C., & Yang, P. (2017). Association of single nucleotide polymorphisms in the 5' upstream region of the C4BPA gene with essential hypertension in a northeastern Han Chinese population. Molecular medicine reports, 16(2), 1289-1297.

[9] Matheu, A., Maraver, A., Collado, M., Garcia-Cao, I., Cañamero, M., Borras, C., … & Serrano, M. (2009). Anti-aging activity of the Ink4/Arf locus. Aging cell, 8(2), 152-161.

[10] Qi, L., Ma, J., Qi, Q., Hartiala, J., Allayee, H., & Campos, H. (2011). Genetic risk score and risk of myocardial infarction in Hispanics. Circulation, 123(4), 374-380.

[11] Rao, S. S., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., … & Aiden, E. L. (2014). A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell, 159(7), 1665-1680.

[12] Rezazadeh, M., Gharesouran, J., Moradi, M., Noroozi, R., Omrani, M. D., Taheri, M., & Ghafouri-Fard, S. (2018). Association Study of ANRIL Genetic Variants and Multiple Sclerosis. Journal of molecular neuroscience: MN, 65(1), 54-59.

[13] Roberts, R., & Stewart, A. F. (2012). Genetics of coronary artery disease in the 21st century. Clinical cardiology, 35(9), 536-540.

[14] Saade, S., Cazier, J. B., Ghassibe-Sabbagh, M., Youhanna, S., Badro, D. A., Kamatani, Y., … & Platt, D. E. (2011). Large scale association analysis identifies three susceptibility loci for coronary artery disease. PloS one, 6(12), e29427.

[15] Severino, P., D'Amato, A., Netti, L., Pucci, M., De Marchis, M., Palmirotta, R., … & Fedele, F. (2018). Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels. International journal of molecular sciences, 19(3), 802.

[16] Tang, S. S., Cheng, J., Cai, M. Y., Yang, X. L., Liu, X. G., Zheng, B. Y., & Xiong, X. D. (2016). Association of lincRNA-p21 Haplotype with Coronary Artery Disease in a Chinese Han Population. Disease markers, 2016, 9109743.

[17] Tsai, M. C., Spitale, R. C., & Chang, H. Y. (2011). Long intergenic noncoding RNAs: new links in cancer progression. Cancer research, 71(1), 3-7.

[18] Wang, K. C., & Chang, H. Y. (2011). Molecular mechanisms of long noncoding RNAs. Molecular cell, 43(6), 904-914.

[19] Wang, Y., Wang, L., Liu, X., Zhang, Y., Yu, L., Zhang, F., … & Wang, X. (2014). Genetic variants associated with myocardial infarction and the risk factors in Chinese population. PloS one, 9(1), e86332.

[20] Xu, B., Fang, Z., He, S., & Wang, J. (2018). ANRIL polymorphism rs4977574 is associated with increased risk of coronary artery disease in Asian populations: A meta-analysis of 12,005 subjects. Medicine, 97(39), e12641. DOI:10.1097/MD.0000000000012641

[21] Yang, C., Tang, R., Ma, X., Wang, Y., Luo, D., Xu, Z., … & Yang, L. (2015). Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric cancer in the Chinese Han population. Oncotarget, 6(17), 15311-15320.

[22] Zhang, F., Zhang, L., & Zhang, C. (2016). Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine, 37(1), 163-175.
How to Cite
Kniazkova, P. V., & Harbuzova, V. Y. (2022). Analysis of the redistribution of rs4977574-polymorphic variants of the ANRIL gen in patients with acute coronary syndrome of different sex. Reports of Vinnytsia National Medical University, 26(1), 108-112.