Original Article

Association of a Novel KIF26B Gene Polymorphism with Susceptibility to Schizophrenia and Breast Cancer: A Case-Control Study

Abstract

Background: KIF26B gene is found to play essential roles in regulating different aspects of cell proliferation and development of the nervous system. We aimed to determine if rs12407427 T/C polymorphism could affect susceptibility to schizophrenia (SZN) and breast cancer (BC), the two genetically correlated diseases.

Methods: The current case-control study was performed from Aug 2018 to Dec 2018. Briefly, 159 female pathologically confirmed BC cases referring to Alzahra Hospital, Isfahan, Iran, and 102 psychologically confirmed SZN patients (60 males and 42 females) admitted to Baharan Hospital, Zahedan, Iran, were enrolled. Using the salting-out method, genomic DNA was extracted, and variants were genotyped using allele-specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method.

Results: The results revealed a significant association between the KIF26B rs12407427 codominant CT (P=0.001), CC (P=0.0001), dominant CT+CC, and recessive CC (P=0.001) genotypes with the risk of developing SZN. Significant correlations were also found regarding rs12407427 and BC susceptibility in different inheritance models, including over-dominant CT (P=0.026), dominant CT+CC (P=0.001), recessive CC (P=0.009), and codominant CT and CC (P=0.001) genotypes. The over-presence of the C allele was also correlated with an increased risk for SZN (P=0.0001) and BC (P=0.0001). Finally, computational analysis predicted that T/C variation in this polymorphism could change the binding sites in proteins involved in splicing.

Conclusion: rs12407427 T/C as a de novo KIF26B variant might be a novel genetic biomarker for SZN and/or BC susceptibility in a sample of the Iranian population.

1. Pritchard JK (2001). Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet, 69(1):124-37.
2. Hirokawa N, Tanaka Y (2015). Kinesin superfamily proteins (KIFs): Various functions and their relevance for important phenomena in life and diseases. Exp Cell Res, 334(1):16-25.
3. Seog D-H, Lee D-H, Lee S-K (2004). Molecular motor proteins of the kinesin superfamily proteins (KIFs): structure, cargo and disease. J Korean Med Sci, 19(1): 1–7.
4. Gu S, Liang H, Qi D, et al (2018). Knockdown of KIF26B inhibits breast cancer cell proliferation, migration, and invasion. Onco Targets Ther, 11: 3195–3203.
5. Heinrich J, Proepper C, Schmidt T, et al (2012). The postsynaptic density protein Abelson interactor protein 1 interacts with the motor protein Kinesin family member 26B in hippocampal neurons. Neuroscience, 221:86-95.
6. Zhang H, Ma R, Wang X, et al (2017). KIF26B, a novel oncogene, promotes proliferation and metastasis by activating the VEGF pathway in gastric cancer. Oncogene, 36(40):5609-5619.
7. Horpaopan S, Spier I, Zink AM, et al (2015). Genome‐wide CNV analysis in 221 unrelated patients and targeted high‐throughput sequencing reveal novel causative candidate genes for colorectal adenomatous polyposis. Int J Cancer, 136(6):E578-89.
8. Teng Y, Guo B, Mu X, Liu S (2018). KIF26B promotes cell proliferation and migration through the FGF2/ERK signaling pathway in breast cancer. Biomed Pharmacother, 108:766-773.
9. Wojcik MH, Okada K, Prabhu SP, et al (2018). De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy. Am J Med Genet A, 176(12):2623-2629.
10. Yang X, Zhang L, Xie L (2018). Upregulation of KIF26B, Cell Migration and Proliferation of Human Ovarian Cancer Cell Lines In Vitro, and Patient Outcomes from Human Bioinformatic Analysis. Med Sci Monit, 24:3863-3872.
11. Szabo L, Morey R, Palpant NJ, et al (2015). Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol, 16(1):126.
12. Bae HA, Mills RA, Lindsay RG, et al (2013). Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus. Invest Ophthalmol Vis Sci, 54(7): 5132–5135.
13. Li X, Bykhovskaya Y, Haritunians T, et al (2012). A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries. Hum Mol Genet, 21(2):421-9.
14. Miller S, Dykes D, Polesky H (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16(3): 1215.
15. Rozen S, Skaletsky H (2000). Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol, 132:365-86.
16. Sanches M, Anna Cristina G, Cristiane S, et al (2015). Nphs2 Mutations Account For Only 15% Of Nephrotic Syndrome Cases. BMC Med Genet, 16:88.
17. Crooks GE, Hon G, Chandonia J-M, Brenner SE (2004). WebLogo: a sequence logo generator. Genome Res, 14(6):1188-90.
18. Sargazi S, Galavi H, Zarei S (2018). Evaluation of attenuative effect of tert‑butylhydroquinone against diazinon‑induced oxidative stress on hematological indices in male Wistar rats. Biomed Rep, 8(6): 565–570.
19. Velligan DI, Alphs LD (2008). Negative symptoms in schizophrenia: the importance of identification and treatment. Psychiatric Times, 25:1-6.
20. Li J, Chen Z, Wang F, et al (2016). Polymorphisms of the TCF4 gene are associated with the risk of schizophrenia in the Han Chinese. Am J Med Genet B Neuropsychiatr Genet, 171(8):1006-1012.
21. Singh B, Chaudhuri TK (2014). Role of C-reactive protein in schizophrenia: an overview. Psychiatry Res, 216(2):277-85.
22. Omrani M, Hashemi M, Eskandari-Nasab E, et al (2014). hsa-mir-499 rs3746444 gene polymorphism is associated with susceptibility to breast cancer in an Iranian population. Biomark Med, 8(2):259-67.
23. Hashemi M, Eskandari-Nasab E, Fazaeli A, et al (2012). Association between polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer risk in a sample Iranian population. Biomark Med, 6(6):797-803.
24. Wang J, Cui F, Wang X, et al (2015). Elevated kinesin family member 26B is a prognostic biomarker and a potential therapeutic target for colorectal cancer. J Exp Clin Cancer Res, 34(1):13.
25. Wang Q, Zhao Z-B, Wang G, et al (2013). High expression of KIF26B in breast cancer associates with poor prognosis. PLoS One, 8(4):e61640.
26. Frias CP. Systematic RNAi-based screening identifies KIF19 as a regulator of neuronal polarity and axon growth in hippocampal neurons. Focus on the axon: Utrecht University Repository. 85.
27. Rong SS, Ma STU, Yu XT, et al (2017). Genetic associations for keratoconus: a systematic review and meta-analysis. Scientific Reports, 7:4620.
28. Li C, Zheng Y, Qin W, et al (2006). A family-based association study of kinesin heavy chain member 2 gene (KIF2) and schizophrenia. Neurosci Lett, 407(2):151-5.
29. Ratta-apha W, Mouri K, Boku S, et al (2015). A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia. Psychiatry Research, 230:424-429.
30. Wang Z-C, Gao Q, Shi J-Y, et al (2013). Genetic polymorphism of the kinesin-like protein KIF1B gene and the risk of hepatocellular carcinoma. PLoS One, 8(4):e62571.
31. Yang X, Li M, Wang L, et al (2015). Association of KIF21B genetic polymorphisms with ankylosing spondylitis in a Chinese Han population of Shandong Province. Clin Rheumatol, 34(10):1729-36.
32. Lu L, Cancel‐Tassin G, Valeri A, et al (2012). Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG. Prostate, 72(4):410-26.
33. Orloff M, Peterson C, He X, et al (2011). Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA, 306(4):410-9.
Files
IssueVol 50 No 2 (2021) QRcode
SectionOriginal Article(s)
Published2021-02-01
DOI https://doi.org/10.18502/ijph.v50i2.5359
PMCIDPMC7956084
PMID33748005
Keywords
KIF26B Breast cancer Schizophrenia Polymorphism

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
SARGAZI S, HEIDARI NIA M, MIRINEJAD S, MOUDI M, JAFARI SHAHROUDI M, SARAVANI R, VALIAN-BOROJENI S. Association of a Novel KIF26B Gene Polymorphism with Susceptibility to Schizophrenia and Breast Cancer: A Case-Control Study. Iran J Public Health. 50(2):397-406.