The association of ZIC5 gene rs965623242 polymorphism with neural tube defects

Year 2024, Volume: 37 Issue: 2, 248 - 255, 31.05.2024

Ebru Önalan Yasemin Aşkın Tugce Kaymaz Mehmet Saraç Ahmet Kazez Tuğba Süzek Vahit Konar

https://doi.org/10.5472/marumj.1493354

Abstract

Objective: This study aims to evaluate the effects of the rs965623242 reference single nucleotide polymorphism (SNP) on the ZIC5
gene in patients with neural tube defect (NTD).
Patients and Methods: One hundred sixty-eight controls and one hundred sixty-eight NTD patients were included in the study.
Deoxyribonucleic acid (DNA) isolation from peripheral blood samples was carried out for all participants. rs965623242 polymorphic
region was amplified by polymerase chain reaction (PCR) and then sequenced.
Results: In the 5’ untranslated region (UTR) of the first exon, guanine (G) to adenine (A) base change was detected in the 38th base of
NM_033132.5. G to A base change was determined as GG genotype in 117 (69.6%), AG genotype in 30 (17.86%), and AA genotype in
21 (12.5%) patients. In the control group, GG genotype in 107 (63.7%), AG genotype in 23 (13.7%) and AA genotype in 38 (22.7%) were
observed. The statistically significant difference was observed between the NTD and the control groups in ZIC5 genotypes or allele
frequencies [p=0.044, odds ratio (OR)=0.49 (0.27-0.88) and p=0.021, OR=0.65 (0.46-0.93), respectively].
Conclusion: ZIC5 rs965623242 polymorphism may have a protective role in the NTD development in the Eastern Anatolian population,
in Turkey. Although, these findings demonstrate that the rs965623242 polymorphism is associated with NTD, we do not clarify how
its expression is affected during the embryonic period and ongoing processes. We will need advanced ongoing genetic and clinical
studies to obtain more detail.

Keywords

Congenital anomalies, Neural tube defect, Spina bifida, ZIC5 gene, Polymorphism

References

• Nikkila A, Rydhström H, Kallen B. The incidence of spina bifida in Sweden 1973-2003: The effect of prenatal diagnosis. Eur J Public Health 2006; 16: 660-2. doi: 10.1093/eurpub/ ckl053.
• Sanri A, Karayel M, Abur U, et al. Frequency and risk factors of neural tube defects in Samsun province. Croat Med J 2018; 40: 413-20. doi:https://doi.org/10.7197/223.vi.441516.
• Tinkle MB, Sterling BS. Neural tube defects: A primary prevention role for nurses. J Obstet Gynecol Neonatal Nurs 1997; 26: 503-23. doi: 10.1111/j.1552-6909.1997.tb02153.x
• Neyzi O, Ertugrul T. 3rd ed. Pediatri 2, Istanbul, Turkey: Nobel Tıp Kitabevleri, 2002:1338-41.
• Akan N. Nöral tüp defektli bebek doğurma riski azaltılabilir. Cumhuriyet Üniversitesi Hemşirelik Yüksekokulu Dergisi 2002; 6: 42-48.
• Brown S, Russo J, Chitayat D, Warburton D. The 13q-syndrome: the molecular definition of a critical deletion region in band 13q32. Am J Hum Genet 1995; 57: 859-66.
• Merzdorf CS. Emerging roles for zic genes in early development. Dev Dyn 2007; 36: 922-40. doi: 10.1002/dvdy.21098.
• Grinberg I, Millen KJ. The ZIC gene family in development and disease. Clin Genet 2005; 67: 290-6. doi: 10.1111/j.1399- 0004.2005.00418
• Elms P, Siggers P, Napper D, Greenfield A, Arkell R. Zic2 is required for neural crest formation and hindbrain patterning during mouse development. Dev Biol 2003; 264: 391-406. doi: 10.1016/j.ydbio.2003.09.005.
• Klootwijk R, Groenen P, Schijvenaars M, et al. Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans. Am J Med Genet 2004; 124A: 40-7. doi: 10.1002/ajmg.a.20402.
• Nagai T, Aruga J, Minowa O, et al. Zic2 regulates the kinetics of neurulation. Proc Natl Acad Sci 2000; 97: 1618-23. doi: 10.1073/pnas.97.4.1618.
• Nakata K, Koyabu Y, Aruga J, Mikoshiba K. A novel member of the Xenopus Zic family, Zic5, mediates neural crest development. Mech Dev 2000; 99 : 83-91. doi: 10.1016/s0925- 4773(00)00480-9.
• Inoue T, Hatayama M, Tohmonda T, Itohara S, Aruga J, Mikoshiba K. Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives. Dev Biol 2004; 270: 146-62. doi: 10.1016/j.ydbio.2004.02.017.
• Ali RG, Bellchambers HM, Arkell RM. Zinc fingers of the cerebellum (Zic): Transcription factors and co-factors. Int J Biochem Cell Biol 2012; 44: 2065-8. doi: 10.1016/j. biocel.2012.08.012.
• Sakai-Kato K, Umezawa Y, Mikoshiba K, Aruga J, Utsunomiya- Tate N. Stability of the folding structure of Zic zinc finger proteins. Biochem Biophys Res Commun 2009; 384: 362-5. doi: 10.1016/j.bbrc.2009.04.151.
• Mizugishi K, Aruga J, Nakata K, Mikoshiba K. Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins. J Biol Chem 2001; 276: 2180-8. doi: 10.1074/jbc.M004430200.
• ZIC5 gene, https://www.ensembl.org/Homo_sapiens/Gene/ Summary?g=ENSG000.001.39800;r=13:99962.964.99971767 ;t=ENST000.002.67294, 05.02.2023
• Primer design, https://eu.idtdna.com/pages, 02.03.2011
• Zhang Y, Liu T, Meyer CA, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol 2008; 9: R137. doi: 10.1186/ gb-2008-9-9-r137.
• ZIC5 gene, rs965623242, http://diana.imis.athenai nnov at i on. g r / D i anaTo ol s / i n d e x . php ? r = s i t e / page&view=software),referans, 22.05.2020
• miRNA binding site, http://mirdb.org/, 22.05.2020
• ZIC5 gene, rs965623242, https://www.internationalgenome. org/, 21.10.2020
• ZIC5 gene, rs965623242, https://exac.broadinstitute.org/, 22.11.2020
• ZIC5 gene, rs965623242, https://www.ncbi.nlm.nih.gov/snp/, 25.11.2020
• ZIC5 gene, rs965623242, https://www.ncbi.nlm.nih.gov/ variation/view/, 25.11.2020
• ZIC5 gene, rs965623242, https://www.ncbi.nlm.nih.gov/snp/ rs965623242#history, 25.11.2020
• Brown LY, Hodge SE, Johnson WG, Guy SG, Nye JS, Brown S. Possible association of NTDs with a polyhistidine tract polymorphism in the ZIC2 gene. Am J Med Genet 2002; 108: 128-31. doi: 10.1002/ajmg.10221.
• Costa-Lima MA, Meneses HN, El-Jaick KB, Amorim MR, Castilla EE, Orioli IM. No association of the polyhistidine tract polymorphism of the ZIC2 gene with neural tube defects in a South American (ECLAMC) population. Mol Med Rep 2008; 1: 443-6.
• Shaikh TH, Haldeman-Englert C, Geiger EA, Ponting CP, Webber C. Genes and biological processes commonly disrupted in rare and heterogeneous developmental delay syndromes. Hum Mol Genet 2011; 20:880-93.
• Mou JT, Huang SX, Yu LL, Xu J, Deng QL, Xie YS, Deng K. Identification of genetic polymorphisms in unexplained recurrent spontaneous abortion based on whole exome sequencing. Ann Transl Med 2022; 10: 603. doi: 10.21037/ atm-22-2179.
• Wang L, Shen H, Liu H, Guo G. Mixture SNPs effect on phenotype in genome-wide association studies. BMC Genom 2015; 16: 3. doi: 10.1186/1471-2164-16-3.
• Botto LD, Moore AC, Khory MJ, Erickson DJ. Neural-tube defects. N Eng J Med 1999; 1509-19.
• Dong C, Li X, Li K, Zheng C, Ying J. The expression pattern of ZIC5 and its prognostic value in lung cancer. Cancer Biother Radiopharm 2021; 36: 407-11.
• Zhao Z, Wang L, Bartom E, et al. Beta-Catenin/ Tcf7l2- dependent transcriptional regulation of GLUT1 gene expression by Zic family proteins in colon cancer. Sci Adv 2019; 5: eaax0698.
• Satow R, Inagaki S, Kato C, Shimozawa M, Fukami K. Identification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells. Cancer Sci 2017; 108: 2405-12.
• Sun Q, Shi R, Wang X, Li D, Wu H, Ren B. Overexpression of ZIC5 promotes proliferation in non-small cell lung cancer. Biochem Biophys Res Commun 2016; 479: 502-9.
• Liu L, Hu X, Sun D, Wu Y, Zhao Z. ZIC5 facilitates the growth of hepatocellular carcinoma through activating Wnt/betacatenin pathway. Biochem Biophys Res Commun 2018; 503: 2173-9.
• Maimaiti A, Aizezi A, Anniwaer J, Ayitula, Ali B, Dilixiati M. Zinc finger of the cerebellum 5 promotes colorectal cancer cell proliferation and cell cycle progression through enhanced CDK1/CDC25c signaling. Arch Med Sci 2021; 17:449-61.
• Nyholm MK, Wu SF, Dorsky RI, Grinblat Y. The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum. Development 2007; 134: 735-46. doi: 10.1242/dev.02756.
• Shi Y, Li J, Chen C, et al. Ketamine modulates Zic5 expression via the Notch signaling pathway in neural crest induction. Front Mol Neurosci 2018; 11: 9. doi: 10.3389/fnmol.2018.00009. https://topmed.nhlbi.nih.gov/topmed-whole-genomesequencing- project-freeze-5b-phases-1-and-2 Accessed https://www.ncbi.nlm.nih.gov/snp/docs/gsr/alfa/
• [43] Excoffier L, Ray N. Surfing during population expansions promotes genetic revolutions and structuration. Trends Ecol Evol 2008; 23: 347-51. doi: 10.1016/j.tree.2008.04.004.
• Hofer T, Ray N, Wegmann D, Excoffier L. Large allele frequency differences between human continental groups are more likely to have occurred by drift during range expansions than by selection. Ann Hum Genet 2009; 73: 95-108. doi: 10.1111/j.1469-1809.2008.00489.x.
• Novembre J, Di Rienzo A. Spatial patterns of variation due to natural selection in humans. Nature Reviews Genetics 2009; 10: 745-55. doi: 10.1038/nrg2632.