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.

Keywords: Breast cancer; KIF26B; Polymorphism; Schizophrenia.

Fig. 1:

rs12407427 C/T genotyping by allele-specific amplified refractory mutation system (ARMS)-PCR resolved on a 2% agarose gel in SZN (A), and BC (B) samples. 467 bp band represents the control amplicon whereas 279 bp amplicon represents both T and C allele-specific bands

Fig. 2:

In silico analysis using splice Aid2 database to predict the possible effects of rs12407427 T/C polymorphism on gene splicing. It has been shown that one splice site was created by the C allele of this variant and other binding sites was broke by the T allele

Fig. 3:

Using Weblogo database to compare the conservation of rs12407427 T/C polymorphism between the different organisms. Both T and C alleles of this variant has low genetic diversity between human and other primates