ABSTRACT
OBJECTIVE: This study seeks to elucidate the association between HLA-A, HLA-B, and HLA-DRB1 alleles and their relative risk contributions to ALL within an Iranian cohort. METHODS: Utilizing a robust case-control design, this research involved 71 ALL patients and 71 age and sex-matched healthy individuals. Genotyping of specified HLA alleles was performed using the advanced PCR-SSP technique. RESULTS: Our findings reveal a marked increase in the prevalence of the HLA-DRB1*04 allele among patients diagnosed with ALL compared to the control group (P<0.027). Conversely, the alleles HLA-A*26 (P=0.025), HLA-A*33 (P=0.020), and HLA-DRB1*03 (P=0.035) were observed at significantly reduced frequencies within the patient population. CONCLUSION: Our findings highlight HLA-DRB1*04 as a potential genetic marker for increased susceptibility to ALL, while HLA-A*26, HLA-A*33, and HLA-DRB1*03 emerge as protective factors.
Subject(s)
Alleles , Genetic Predisposition to Disease , HLA-A Antigens , HLA-B Antigens , HLA-DRB1 Chains , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Case-Control Studies , HLA-DRB1 Chains/genetics , Female , Male , Iran/epidemiology , HLA-B Antigens/genetics , HLA-A Antigens/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Follow-Up Studies , Adult , Genotype , Adolescent , Child , Young Adult , Child, Preschool , Biomarkers, Tumor/geneticsABSTRACT
BACKGROUND: Acute lymphoblastic leukemia is the most prevailing pediatric hematologic malignancy, and various factors such as environmental exposures and genetic variation affect ALL susceptibility and patients outcome. According to genome-wide association studies, several single nucleotide polymorphisms (SNPs) in IKZF1 (rs4132601) and CDKN2A (rs3731249 and rs3731217) genes are associated with ALL susceptibility. Hereupon, this study aimed to discover the association between these SNPs and the risk of childhood ALL among a sample of the Iranian population. METHODS: A total of fifty children with ALL were included in this case-control study, along with an additional fifty healthy children, matched for age and gender. High-resolution melting (HRM) analysis was employed to genotyping rs4132601, rs3731249, and rs3731217. RESULTS: In the patient group, the CT genotype and T allele frequency of rs3731249 were significantly greater than controls (p = 0.01 and p = 0.005, respectively). Moreover, the positive association of CT and dominant model (CT + TT) genotypes and T allele at rs3731249 with the risk of ALL was confirmed (OR = 9.56, OR = 10.76 and OR = 11.00, respectively). There was no significant relation between rs4132601 (IKZF1), rs3731217 (CDKN2A), and childhood ALL. CONCLUSION: The present study indicates that CT genotype and T allele at rs3731249 (CDKN2A) can significantly increase the risk of ALL among children.