Investigation of ELF5, KIF18A, NPTX1 and COL23A1 genes in the pathophysiology of indirect inguinal hernia

INVESTIGATION OF ELF5, KIF18A, NPTX1 AND COL23A1 GENES IN THE PATHOPHYSIOLOGY OF INDIRECT INGUINAL HERNIA Indirect inguinal hernia (IIH); It occurs as a result of intra-abdominal organs entering the processus vaginalis (PV) which remains open due to the fact that the PV formed during the descent of the testis to the scrotum during the fetal period does not close despite the completion of the descent of the testis. If left untreated, there is a possibility of tissue, organ loss and life-threatening. The patency of PV, which causes IIH, develops multifactorially under the influence of environmental and genetic factors. Although genetic factors are thought to play an important role in the etiology of indirect innguinal hernia, there are not enough studies on this subject yet. In our study, we aimed to investigate the effect of genetic factors in the etiology of IIH. Results were evaluated with SPSS 22. The study group consisted of 186 patients who were operated on due to IIH in the Fırat University Pediatric Surgery Clinic, and 26 patients with undescended testicle as the control group. Quantitative mRNA level analyzes were performed in the presence of relevant primers belonging to ELF5, KIF18A, NPTX1 and COL23A1 genes by RNA isolation from blood and PV tissues in both groups. With ELISA analysis, the protein level of KIF18A, which has the highest gene expression in tissue samples, was examined. In our study, 8.6% of the patient group had a family history of inguinal hernia (IH). In genetic evaluation, the results of polymorphism variants of ELF5 (p<0.001), KIF18A (p<0.004) and COL23A1 (p<0.001) genes in the study group were found to be significantly higher than the control group. NPTX1 (p=0.712) values were insignificant between groups. There was no significant difference in the level of KIF18A (p=0.972) protein compared to the control group. The increase in the gene polymorphism of KIF18A suggests that it plays a role in the control of cell division. It has been shown that the increase in KIF18A is necessary for cell division and increases in various cancer types. First, histopathological evaluations with H&E showed a significant increase in proliferation in both smooth muscle cells (SMC; smooth musle cell) and mesothelial cells in childhood IH compared to control. These SMCs are indicators of impaired apoptotic processes. In addition, it was shown that the expression of Proliferating Cell Nuclear Antigen, another marker of cell division, increased in IH groups compared to the control. Our data lead to the conclusion that KIF18A increases in parallel with the increase in cell division in IH tissues. Another gene that we found increased expression in our study is COL23A1. One of the major expression sites of COL23A1 is the skin. Its increased expression has been associated with recurrence and metastasis of prostate cancer, implying the presence of the extracellular matrix cycle. In support of this data, it has been shown that cell division is increased at the tissue level in IH cases. Our findings in our study show that the increase in COL23A1 may accompany increased cell division. Misexpression of the ELF5 gene can impair the specification and differentiation of epithelial cells, thus it is likely involved in the epithelial-mesenchymal transition (EMT) process, which is a notable feature of scrotal hernia etiology. In a study, it was shown that increased expression of mesothelial HBME-1, a mesothelial cell marker, was a significant immunohistochemically increase in IH groups compared to peritoneal and PV samples. Therefore, the increase in ELF5 in our findings can be explained by the increase in EMT in IH patients. According to the results of the study; ELF5, KIF18A and COL23A1 genes can be counted among the effective factors in PV closure. However, we think that there is a need for more comprehensive studies with more patients or animal studies, in which other genes are studied, and these studies will be useful in illuminating the etiology of IIH. Keywords: Genetics, polymorphism, inguinal hernia, children, ELF5, KIF18A, NPTX1 and COL23A1