Main Article Content
Abstract
Hypertension in pregnancy (HIP) affects approximately 10% of all pregnant women worldwide, including preeclampsia, eclampsia, gestational hypertension, and chronic hypertension. This study aims to analyze the potential of the Fibrinogen Like Protein 1 (FGL1) gene in increasing the risk of liver side effects due to the use of Nifedipine in pregnant women with genomic and bioinformatic information approaches. Bioinformatic databases included GWAS and SNPnexus, and gene expression profiles were examined using the GTEx Portal. We prioritized SNPs based on Benign, Possibly damaging, and Probably damaging criteria with the polyphen scoring system. Of the two SNPs (rs167479 and rs2653414) identified, the rs2653414 variant in the FGL1 gene showed probably damaging properties. The results showed that rs2653414 encoding the FGL1 gene has the potential to worsen the condition of hypertension during pregnancy and impact the side effects of using Nifedipine. FGL1 plays a role in liver regeneration, lipid metabolism, and energy utilization. Nifedipine metabolized in the liver can cause hepatitis with severe clinical symptoms. Therefore, routine monitoring of liver function in gestational hypertensive patients receiving Nifedipine therapy is necessary.
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References
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- Wang, J., Sanmamed, M. F., Datar, I., Su, T. T., Ji, L., Sun, J., Chen, L., Chen, Y., Zhu, G., Yin, W., Zheng, L., Zhou, T., Badri, T., Yao, S., Zhu, S., Boto, A., Sznol, M., Melero, I., Vignali, D. A. A., Chen, L. (2019). Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell, 176(1–2), 334-347.e12. https://doi.org/10.1016/j.cell.2018.11.010
- WHO recommendations for Prevention and treatment of pre-eclampsia and eclampsia. (2011)
- Yudhani, R. D., Pakha, D. N., Suyatmi, S., & Irham, L. M. (2023). Identifying pathogenic variants related to systemic lupus erythematosus by integrating genomic databases and a bioinformatic approach. Genomics and Informatics, 21(3). https://doi.org/10.5808/gi.23002
- Yusuf, D., Christy, J., Owen, D., Ho, M., Li, D., & Fishman, M. J. (2018). A case report of nifedipine-induced hepatitis with jaundice. BMC Research Notes, 11(1). https://doi.org/10.1186/s13104-018-3322-9
- Zhang, Y., Qiao, H. X., Zhou, Y. T., Hong, L., & Chen, J. H. (2018). Fibrinogen-like-protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis. Molecular Medicine Reports, 18(2), 1465–1472. https://doi.org/10.3892/mmr.2018.9097
References
Adebiyi, E., Adam, Y., Samtal, C., Brandenburg, J. tristan, & Falola, O. (2021). Performing post-genome-wide association study analysis: Overview, challenges and recommendations. F1000Research, 10.https://doi.org/10.12688/f1000research.53962.1
Amukti, D.P., Wazni, A. R., Irham, L, M., Sulistyani, N., Ma’ruf, M., Adikusuma, W., Sarasmita, M.A., Khairi S., Purwanto, B. D, Suyatmi, S., Siswanto, L. M. H., & Chong, R. (2024) ‘Identifying pathogenic variants associated with Alzeimer by integrating genomic databases and bioinformatics approaches’, E3S Web of Conferences, 501. Available at: https://doi.org/10.1051/e3sconf/202450101021.
Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013). Predicting functional effect of human missense mutations using PolyPhen-2. Current Protocols in Human Genetics, SUPPL.76. https://doi.org/10.1002/0471142905.hg0720s76
Alatas, H. (n.d.). Hipertensi pada Kehamilan. In Herb-Medicine Journal.
Demchev, V., Malana, G., Vangala, D., Stoll, J., Desai, A., Kang, H. W., Li, Y., Nayeb-Hashemi, H., Niepel, M., Cohen, D. E., & Ukomadu, C. (2013). Targeted Deletion of Fibrinogen Like Protein 1 Reveals a Novel Role in Energy Substrate Utilization. PLoS ONE, 8(3). https://doi.org/10.1371/journal.pone.0058084
Irham, L. M., Adikusuma, W., Lolita, L., Puspitaningrum, A. N., Afief, A. R., Sarasmita, M. A., Dania, H., Khairi, S., Djalilah, G. N., Purwanto, B. D., & Chong, R. (2023). Investigation of susceptibility genes for chickenpox disease across multiple continents. Biochemistry and Biophysics Reports, 33. https://doi.org/10.1016/j.bbrep.2022.101419
Iryaningrum, M. R., Yuwono, A., & Cahyadi, A. (2023). Desember 2023: hal. In Damianus Journal of Medicine (Vol. 22, Issue 3).
Johnson, T. A., Jinnah, H. A., & Kamatani, N. (2019). Shortage of cellular ATP as a cause of diseases and strategies to enhance ATP. Frontiers in Pharmacology, 10(FEB). https://doi.org/10.3389/fphar.2019.00098
Jung, T. W., Chung, Y. H., Kim, H. C., Abd El-Aty, A. M., & Jeong, J. H. (2018). Hyperlipidemia-induced hepassocin in the liver contributes to insulin resistance in skeletal muscle. Molecular and Cellular Endocrinology, 470, 26–33. https://doi.org/10.1016/j.mce.2017.10.014
Magee, L. A., Brown, M. A., Hall, D. R., Gupte, S., Hennessy, A., Karumanchi, S. A., Kenny, L. C., McCarthy, F., Myers, J., Poon, L. C., Rana, S., Saito, S., Staff, A. C., Tsigas, E., & von Dadelszen, P. (2022). The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertension, 27, 148–169. https://doi.org/10.1016/j.preghy.2021.09.008
Makinde, E., Ma, L., Mellick, G. D., & Feng, Y. (2023). Mitochondrial Modulators: The Defender. In Biomolecules (Vol. 13, Issue 2). MDPI. https://doi.org/10.3390/biom13020226
Martinova, V., & Yusrizal, F. (2021). Hubungan Kadar Serum Klotho Dengan Kejadian Preeklamsia (Association Of Serum Klotho Levels With The Incidence Of Preeclampsia). 6(12). https://doi.org/10.36418/Syntax-Literate.v6i12.5174
Mubarak Babeker, M., Mohamed Suliman Albakry, A., Nagm Eldin Elsamani, M., Mossalami, G., Abdelaziz Elnasri, H., & Abdelrahman Mohamed Khaier, M. (2019). In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human <i>MPL</i> Gene. International Journal of Genetics and Genomics, 7(4), 124. https://doi.org/10.11648/j.ijgg.20190704.17
Nayeb-Hashemi, H., Desai, A., Demchev, V., Bronson, R. T., Hornick, J. L., Cohen, D. E., & Ukomadu, C. (2015). Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development. Biochemical and Biophysical Research Communications, 465(2), 167–173. https://doi.org/10.1016/j.bbrc.2015.07.078
Pakha, D.N., Yudhani, R.D. and Irham, L.M. (2024) ‘Investigation of missense mutation-related type 1 diabetes mellitus through integrating genomic databases and bioinformatic approach’, Genomics and Informatics, 22(1). Available at: https://doi.org/10.1186/s44342-024-00005-4.
Paulina, A.J. et al. (2024) ‘Genetic-driven biomarkers for liver fibrosis through bioinformatic approach’, Egyptian Journal of Medical Human Genetics, 25(1). Available at: https://doi.org/10.1186/s43042-024-00528-z.
Piórkowska, K., Żukowski, K., Ropka-Molik, K., & Tyra, M. (2022). Variations in Fibrinogen-like 1 (FGL1) Gene Locus as a Genetic Marker Related to Fat Deposition Based on Pig Model and Liver RNA-Seq Data. Genes, 13(8). https://doi.org/10.3390/genes13081419
Sharma, R., Kapoor, B., & Verma, U. (n.d.). DRUG UTILIZATION PATTERN DURING PREGNANCY IN NORTH INDIA.
Snider, M. E., Nuzum, D. S., & Veverka, A. (2008). Long-acting nifedipine in the management of the hypertensive patient. In Vascular Health and Risk Management (Issue 6).
Turana, Y., Tengkawan, J., & Soenarta, A. A. (2020). Asian management of hypertension: Current status, home blood pressure, and specific concerns in Indonesia. In Journal of Clinical Hypertension (Vol. 22, Issue 3, pp. 483–485). Blackwell Publishing Inc. https://doi.org/10.1111/jch.13681
Ulku Terzi, Ilker Ates, Abdulsamet Erden et al. Investigation of the Pathogenic Variants Induced Sjogren’s Syndrome in Turkish Population. (2024). PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-3978557/v1
Uzieliene, I., Bernotiene, E., Rakauskiene, G., Denkovskij, J., Bagdonas, E., Mackiewicz, Z., Porvaneckas, N., Kvederas, G., & Mobasheri, A. (2019). The Antihypertensive Drug Nifedipine Modulates the Metabolism of Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells. Frontiers in Endocrinology, 10. https://doi.org/10.3389/fendo.2019.00756
Qin, D. (2019). Next-generation sequencing and its clinical application. Cancer Biology & Medicine, 16(1), 4-10. https://doi.org/10.20892/j.issn.2095-3941.2018.0055
Wang, J., Sanmamed, M. F., Datar, I., Su, T. T., Ji, L., Sun, J., Chen, L., Chen, Y., Zhu, G., Yin, W., Zheng, L., Zhou, T., Badri, T., Yao, S., Zhu, S., Boto, A., Sznol, M., Melero, I., Vignali, D. A. A., Chen, L. (2019). Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell, 176(1–2), 334-347.e12. https://doi.org/10.1016/j.cell.2018.11.010
WHO recommendations for Prevention and treatment of pre-eclampsia and eclampsia. (2011)
Yudhani, R. D., Pakha, D. N., Suyatmi, S., & Irham, L. M. (2023). Identifying pathogenic variants related to systemic lupus erythematosus by integrating genomic databases and a bioinformatic approach. Genomics and Informatics, 21(3). https://doi.org/10.5808/gi.23002
Yusuf, D., Christy, J., Owen, D., Ho, M., Li, D., & Fishman, M. J. (2018). A case report of nifedipine-induced hepatitis with jaundice. BMC Research Notes, 11(1). https://doi.org/10.1186/s13104-018-3322-9
Zhang, Y., Qiao, H. X., Zhou, Y. T., Hong, L., & Chen, J. H. (2018). Fibrinogen-like-protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis. Molecular Medicine Reports, 18(2), 1465–1472. https://doi.org/10.3892/mmr.2018.9097