Association of the lncRNA HOTAIR Gene rs4759314 with Susceptibility to Recurrent Spontaneous Abortion in a Chinese Han Population

This study was to examine the association between the long noncoding RNA (lncRNA) HOTAIR polymorphism (rs4759314, rs4759314) and the risk of recurrent spontaneous abortion (RSA) in Chinese Han women. 378 women with RSA and 361 pregnant women with normal pregnancies were selected as study subjects. T...

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Published inThe Tohoku Journal of Experimental Medicine Vol. 266; no. 3; pp. 229 - 235
Main Authors Luo, Binglai, Liu, Xiaoli, Huang, Jiangang, Wang, Jinyong
Format Journal Article
LanguageEnglish
Published Japan Tohoku University Medical Press 2025
Subjects
Online AccessGet full text
ISSN0040-8727
1349-3329
1349-3329
DOI10.1620/tjem.2024.J084

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Abstract This study was to examine the association between the long noncoding RNA (lncRNA) HOTAIR polymorphism (rs4759314, rs4759314) and the risk of recurrent spontaneous abortion (RSA) in Chinese Han women. 378 women with RSA and 361 pregnant women with normal pregnancies were selected as study subjects. The expression level of lncRNA HOTAIR was detected by fluorescence quantitative PCR. PCR restriction fragment length polymorphism (PCR-RFLP) method was used to detect genotyping. Logistic regression analysis was used to assess the independent factors of HOTAIR rs4759314 affecting recurrent miscarriage. The lncRNA HOTAIR gene expression level was significantly reduced in RSA patients. Rs1899663 polymorphism and rs4759314 GG genotype do not significantly increase the risk of developing RSA (P > 0.050). Rs4759314 AG genotype and rs4759314G allele significantly increased the risk of developing RSA (P < 0.050). Logistic analysis showed a significant correlation between rs4759314 and the occurrence of RSA (OR = 0.367, 95% CI = 0.232-0.580, P < 0.050). The lncRNA HOTAIR rs4759314 locus may serve as a biomarker for RSA susceptibility in the Chinese Han population.
AbstractList This study was to examine the association between the long noncoding RNA (lncRNA) HOTAIR polymorphism (rs4759314, rs4759314) and the risk of recurrent spontaneous abortion (RSA) in Chinese Han women. 378 women with RSA and 361 pregnant women with normal pregnancies were selected as study subjects. The expression level of lncRNA HOTAIR was detected by fluorescence quantitative PCR. PCR restriction fragment length polymorphism (PCR-RFLP) method was used to detect genotyping. Logistic regression analysis was used to assess the independent factors of HOTAIR rs4759314 affecting recurrent miscarriage. The lncRNA HOTAIR gene expression level was significantly reduced in RSA patients. Rs1899663 polymorphism and rs4759314 GG genotype do not significantly increase the risk of developing RSA (P > 0.050). Rs4759314 AG genotype and rs4759314G allele significantly increased the risk of developing RSA (P < 0.050). Logistic analysis showed a significant correlation between rs4759314 and the occurrence of RSA (OR = 0.367, 95% CI = 0.232-0.580, P < 0.050). The lncRNA HOTAIR rs4759314 locus may serve as a biomarker for RSA susceptibility in the Chinese Han population.
ArticleNumber 2024.J084
Author Jiangang Huang
Jinyong Wang
Xiaoli Liu
Binglai Luo
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Keywords rs4759314
long noncoding RNA HOTAIR
single nucleotide polymorphisms
recurrent spontaneous abortion
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Daher, S., Mattar, R., Gueuvoghlanian-Silva, B.Y. & Torloni, M.R.(2012) Genetic polymorphisms and recurrent spontaneous abortions: an overview of current knowledge. Am. J. Reprod. Immunol., 67, 341-347.
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Volkohon, A.D., Kolnoguz, A.V., Chumachenko, Y.D., Harbuzova, V.Y. & Tsyndrenko, N.L.(2020) Association analysis between HOTAIR RS1899663 single nucleotide polymorphism and clear cell renal cell carcinoma development in Ukrainian population. Wiad. Lek., 73, 12-16.
Kim, J.O., Jun, H.H., Kim, E.J., Lee, J.Y., Park, H.S., Ryu, C.S., Kim, S., Oh, D., Kim, J.W. & Kim, N.K.(2020) Genetic Variants of HOTAIR Associated With Colorectal Cancer Susceptibility and Mortality. Front. Oncol., 10, 72.
Li, Y., Zhao, W., Shi, R., Jia, J., Li, X. & Cheng, J.(2018) Rs4759314 polymorphism located in HOTAIR is associated with the risk of congenital heart disease by alternating downstream signaling via reducing its expression. J. Cell Biochem., 119, 8112-8122.
Zhang, X., Zhou, L., Fu, G., Sun, F., Shi, J., Wei, J., Lu, C., Zhou, C., Yuan, Q. & Yang, M.(2014) The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis, 35, 2062-2067.
Barbaro, G., Inversetti, A., Cristodoro, M., Ticconi, C., Scambia, G. & Di Simone, N.(2023) HLA-G and Recurrent Pregnancy Loss. Int. J. Mol. Sci., 24, 2557.
Guo, W., Dong, Z., Bai, Y., Guo, Y., Shen, S., Kuang, G. & Xu, J.(2015) Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol., 36, 2845-2854.
Kim, H.J., Lee, D.W., Yim, G.W., Nam, E.J., Kim, S., Kim, S.W. & Kim, Y.T.(2015) Long non-coding RNA HOTAIR is associated with human cervical cancer progression. Int. J. Oncol., 46, 521-530.
Minas, V., Jeschke, U., Kalantaridou, S.N., Richter, D.U., Reimer, T., Mylonas, I., Friese, K. & Makrigiannakis, A.(2007) Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin. Mol. Hum. Reprod., 13, 663-673.
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Salimi, S., Sargazi, S., Heidari Nia, M., Mirani Sargazi, F. & Ghasemi, M.(2021) Genetic variants of HOTAIR are associated with susceptibility to recurrent spontaneous abortion: A preliminary case-control study. J. Obstet. Gynaecol. Res., 47, 3767-3778.
Pan, W., Liu, L., Wei, J., Ge, Y., Zhang, J., Chen, H., Zhou, L., Yuan, Q., Zhou, C. & Yang, M.(2016) A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol. Carcinog., 55, 90-96.
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Wang, H., Qin, R., Guan, A., Yao, Y., Huang, Y., Jia, H., Huang, W. & Gao, J.(2018a) HOTAIR enhanced paclitaxel and doxorubicin resistance in gastric cancer cells partly through inhibiting miR-217 expression. J. Cell. Biochem., 119, 7226-7234.
Park, H.W., Kim, Y.R., Lee, J.Y., Ko, E.J., Kwon, M.J., Kim, J.H. & Kim, N.K.(2022) Association of Polymorphisms in the Long Non-Coding RNA HOTAIR with Recurrent Pregnancy Loss in a Korean Population. Genes (Basel), 13, 2138.
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References_xml – reference: Kopp, F. & Mendell, J.T.(2018) Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell, 172, 393-407.
– reference: Zhang, Y. & Wang, S.(2022) The possible role of long non-coding RNAs in recurrent miscarriage. Mol. Biol. Rep., 49, 9687-9697.
– reference: Guo, L., Lu, X., Zheng, L., Liu, X. & Hu, M.(2016) Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population. PLoS One, 11, e0160039.
– reference: Qiu, H., Liu, Q., Li, J., Wang, X., Wang, Y., Yuan, Z., Li, J. & Pei, D.S.(2016) Analysis of the association of HOTAIR single nucleotide polymorphism (rs920778) and risk of cervical cancer. APMIS, 124, 567-573.
– reference: Wang, L.P., Wang, J.P. & Wang, X.P.(2018b) HOTAIR contributes to the growth of liver cancer via targeting miR-217. Oncol. Lett., 15, 7963-7972.
– reference: Van Der Ven, K.(2015) Recurrent spontaneous miscarriage. Update on diagnosis and treatment. Gynakologische Praxis, 39, 423-434.
– reference: Han, L., Zhang, H.C., Li, L., Li, C.X., Di, X. & Qu, X.(2018) Downregulation of Long Noncoding RNA HOTAIR and EZH2 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Breast Cancer Cells. Cancer Biother. Radiopharm., 33, 241-251.
– reference: Huppertz, B.(2019) Traditional and New Routes of Trophoblast Invasion and Their Implications for Pregnancy Diseases. Int. J. Mol. Sci., 21, 289.
– reference: Li, Y., Zhao, W., Shi, R., Jia, J., Li, X. & Cheng, J.(2018) Rs4759314 polymorphism located in HOTAIR is associated with the risk of congenital heart disease by alternating downstream signaling via reducing its expression. J. Cell Biochem., 119, 8112-8122.
– reference: Salimi, S., Sargazi, S., Heidari Nia, M., Mirani Sargazi, F. & Ghasemi, M.(2021) Genetic variants of HOTAIR are associated with susceptibility to recurrent spontaneous abortion: A preliminary case-control study. J. Obstet. Gynaecol. Res., 47, 3767-3778.
– reference: Practice Committee of the American Society for Reproductive Medicine (2012) Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil. Steril., 98, 1103-1111.
– reference: Iacoviello, M., Monitillo, F., Leone, M., Citarelli, G., Doronzo, A., Antoncecchi, V., Puzzovivo, A., Rizzo, C., Lattarulo, M.S., Massari, F., Caldarola, P. & Ciccone, M.M.(2016) The Renal Arterial Resistance Index Predicts Worsening Renal Function in Chronic Heart Failure Patients. Cardiorenal Med., 7, 42-49.
– reference: Wang, H., Qin, R., Guan, A., Yao, Y., Huang, Y., Jia, H., Huang, W. & Gao, J.(2018a) HOTAIR enhanced paclitaxel and doxorubicin resistance in gastric cancer cells partly through inhibiting miR-217 expression. J. Cell. Biochem., 119, 7226-7234.
– reference: Abdi, E. & Latifi-Navid, S.(2022) Emerging long noncoding RNA polymorphisms as novel predictors of survival in cancer. Pathol. Res. Pract., 239, 154165.
– reference: Guo, W., Dong, Z., Bai, Y., Guo, Y., Shen, S., Kuang, G. & Xu, J.(2015) Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol., 36, 2845-2854.
– reference: Zhang, X., Zhou, L., Fu, G., Sun, F., Shi, J., Wei, J., Lu, C., Zhou, C., Yuan, Q. & Yang, M.(2014) The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis, 35, 2062-2067.
– reference: Zhang, Y., Zhang, K., Luo, Z., Liu, L., Wu, L. & Liu, J.(2016) Circulating long non-coding HOX transcript antisense intergenic ribonucleic acid in plasma as a potential biomarker for diagnosis of breast cancer. Thorac. Cancer, 7, 627-632.
– reference: Park, H.W., Kim, Y.R., Lee, J.Y., Ko, E.J., Kwon, M.J., Kim, J.H. & Kim, N.K.(2022) Association of Polymorphisms in the Long Non-Coding RNA HOTAIR with Recurrent Pregnancy Loss in a Korean Population. Genes (Basel), 13, 2138.
– reference: Barbaro, G., Inversetti, A., Cristodoro, M., Ticconi, C., Scambia, G. & Di Simone, N.(2023) HLA-G and Recurrent Pregnancy Loss. Int. J. Mol. Sci., 24, 2557.
– reference: Daher, S., Mattar, R., Gueuvoghlanian-Silva, B.Y. & Torloni, M.R.(2012) Genetic polymorphisms and recurrent spontaneous abortions: an overview of current knowledge. Am. J. Reprod. Immunol., 67, 341-347.
– reference: Li, H., Tang, X.M., Liu, Y., Li, W., Chen, Q. & Pan, Y.(2017) Association of Functional Genetic Variants of HOTAIR with Hepatocellular Carcinoma (HCC) Susceptibility in a Chinese Population. Cell Physiol. Biochem., 44, 447-454.
– reference: Volkohon, A.D., Kolnoguz, A.V., Chumachenko, Y.D., Harbuzova, V.Y. & Tsyndrenko, N.L.(2020) Association analysis between HOTAIR RS1899663 single nucleotide polymorphism and clear cell renal cell carcinoma development in Ukrainian population. Wiad. Lek., 73, 12-16.
– reference: Pan, W., Liu, L., Wei, J., Ge, Y., Zhang, J., Chen, H., Zhou, L., Yuan, Q., Zhou, C. & Yang, M.(2016) A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol. Carcinog., 55, 90-96.
– reference: Cho, S.H., Kim, J.H., Park, H.W., Park, H.S., An, H.J., Kim, Y.R., Ahn, E.H., Lee, W.S. & Kim, N.K.(2021) Associations between HOTAIR polymorphisms rs4759314, rs920778, rs1899663, and rs7958904 and risk of primary ovarian insufficiency in Korean women. Maturitas, 144, 74-80.
– reference: Kim, H.J., Lee, D.W., Yim, G.W., Nam, E.J., Kim, S., Kim, S.W. & Kim, Y.T.(2015) Long non-coding RNA HOTAIR is associated with human cervical cancer progression. Int. J. Oncol., 46, 521-530.
– reference: Kim, J.O., Jun, H.H., Kim, E.J., Lee, J.Y., Park, H.S., Ryu, C.S., Kim, S., Oh, D., Kim, J.W. & Kim, N.K.(2020) Genetic Variants of HOTAIR Associated With Colorectal Cancer Susceptibility and Mortality. Front. Oncol., 10, 72.
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Snippet This study was to examine the association between the long noncoding RNA (lncRNA) HOTAIR polymorphism (rs4759314, rs4759314) and the risk of recurrent...
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SubjectTerms Abortion, Habitual - genetics
Adult
Case-Control Studies
China
East Asian People - genetics
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
long noncoding RNA HOTAIR
Polymorphism, Single Nucleotide
Pregnancy
recurrent spontaneous abortion
RNA, Long Noncoding - genetics
rs4759314
single nucleotide polymorphisms
Title Association of the lncRNA HOTAIR Gene rs4759314 with Susceptibility to Recurrent Spontaneous Abortion in a Chinese Han Population
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https://www.ncbi.nlm.nih.gov/pubmed/39231728
https://doi.org/10.1620/tjem.2024.j084
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