Associations of XRCC4, eNOS, and PER3 VNTR variants with Childhood Acute Lymphoblastic Leukemia in Turkish Patients

Abstract

Objective: The genetic factors responsible for the etiopathogenesis of childhood acute leukemia have been extensively investigated. High-resolution expression analysis of the whole genome, and results of gene studies including whole genome sequencing, copy number changes of DNA, loss of heterozygosity and epigenetic changes revealed the classification of acute lymphoblastic leukemia (ALL). A variable number of tandem repeats (VNTRs) can regulate many biological processes, including gene transcription, protein function, morphological development, and cancer formation. They may also play a role in many disorders in humans such as labile repeat expansions. In this paper, our aim was to compare the genotype and allele frequencies in VNTR variants of XRCC4, eNOS, and PER3 between pediatric ALL patients and healthy controls. Methods: Seventy-four high-risk pediatric ALL patients (82.4% B-ALL, 17.6% T-ALL) who were consecutively admitted to the Pediatric Hematology Units of İstanbul Medical Faculty and Yeni Yuzyıl Medical Faculty and 100 healthy volunteers were included in this case-control study. VNTRs of three genes were analyzed using the polymerase chain reaction method. Results: The frequency of the eNOS VNTR 4a/4a genotype was found to be higher in the pediatric patients with ALL compared to the healthy controls (p=0.044) and the risk factor for childhood ALL was found to be 8.382 (95% confidence interval =0.985-71.262). The frequency of eNOS 4/a allele was found to be higher in the childhood ALL group compared to the controls (p=0.013). The frequencies of the 5R/5R genotype and 5R allele of the PER3 VNTR were found to be significantly lower in the childhood ALL patients (p=0.039 and p=0.015, respectively). Conclusion: Our results show that functional variants of the eNOS and PER3 genes may have an important relationship with the etiopathogenesis of childhood ALL. Further studies including larger groups and different ethnic populations are needed to determine the effect of VNTR variants on the risk of developing childhood ALL. ©Copyright 2022 by Medical Journal of Bakırköy published by Galenos Yayınevi.