Dataset Information

IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study.

ABSTRACT: BACKGROUND:Associations between IKZF1 gene variants and Acute Lymphoblastic Leukemia (ALL) was recently reported. We examined whether the common IKZF1 polymorphisms rs4132601 T/G and rs111978267 A/G are associated with ALL among a Tunisian pediatric cohort. METHODS:This case-control study involved 170 patients with ALL and 150 control subjects. SNP genotyping was performed by TaqMan® SNP Genotyping Assay. RESULTS:The minor allele G of IKZF1 gene polymorphism rs4132601 T/G was significantly higher in ALL cases than in control subjects (P =?0.029), with 1.54-fold increased risk of ALL. The association of rs4132601 with ALL was seen under co-dominant (P =?0.009), recessive (P =?0.006), and additive (P =?0.027) genetic models, of which the co-dominant (P =?0.027) and recessive (P =?0.027) association remained significant after adjusting for covariates, and False Discovery Rate correction. In contrast, no association was noted for rs111978267 variant. Two-locus (rs4132601-rs11978267) IKZF1 haplotype analysis demonstrated association of GA (P =?0.053), with increased ALL risk [OR (95% CI)?=?1.58 (1.00-2.51)], which remained significant after controlling for key covariates [aP =?0.046; aOR (95% CI)?=?1.61 (1.01-2.57)]. CONCLUSION:We demonstrated the association of IKZF1 polymorphism rs4132601 T/G with increased risk of ALL among Tunisian pediatric cohort, with altered phenotypic changes among ALL patients.

SUBMITTER: Mahjoub S

PROVIDER: S-EPMC6788013 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study.

Mahjoub Sana S Chayeb Vera V Zitouni Hedia H Ghali Rabeb M RM Regaieg Haifa H Almawi Wassim Y WY Mahjoub Touhami T

BMC medical genetics 20191011 1

<h4>Background</h4>Associations between IKZF1 gene variants and Acute Lymphoblastic Leukemia (ALL) was recently reported. We examined whether the common IKZF1 polymorphisms rs4132601 T/G and rs111978267 A/G are associated with ALL among a Tunisian pediatric cohort.<h4>Methods</h4>This case-control study involved 170 patients with ALL and 150 control subjects. SNP genotyping was performed by TaqMan® SNP Genotyping Assay.<h4>Results</h4>The minor allele G of IKZF1 gene polymorphism rs4132601 T/G w ...[more]

PMID: 31604453

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Project description:Background/aimAcute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. METTL14, an N6-methyladenosine (m6A) modification protein, plays several roles in cancer development and is involved in the pathogenesis of various types of cancers. However, the role of METTL14 gene single nucleotide polymorphisms (SNPs) in pediatric ALL susceptibility remains to be investigated.MethodsA case-control design and multinomial logistic regression were used to develop models to estimate the overall risk for pediatric ALL and three METTL14 gene SNPs (rs298982 G/A, rs298981 A/G and rs1064034 T/A) in 808 cases and 1340 controls, which were genotyped using a TaqMan assay. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Furthermore, stratified analysis was performed to explore associations of rs298982 and rs1064034 with pediatric ALL susceptibility in terms of age, sex, immunophenotype, minimal residual disease (MRD), and other clinical characteristics.ResultsAmong the three analyzed SNPs, rs298982 G/A and rs1064034 T/A exhibited a significant association with decreased childhood ALL risk, while rs298981 A/G exhibited no difference. In stratified analysis, rs298982 GA/AA and rs1064034 TA/AA had a protective effect in children <120 months of age and males, common B ALL, TEL-AML, non gene fusion, normal diploid, and high WBC. However, the rs1064034 TA/AA genotype was associated with an increased risk of mixed immunophenotyping. Compared with the reference haplotype GAT, haplotypes CAA, CGT and CGA were significantly associated with elevated ALL risk, while haplotype GGT was significantly associated decreased ALL risk. Moreover, subjects carrying rs298982 A or rs1064034 A exhibited less minimal MRD after induced chemotherapy. Functional annotations revealed that METTL14 gene SNPs rs298982 G/A and rs1064034 T/A could be potential functional variants.ConclusionIn conclusion, METTL14 gene polymorphisms influence the risk of ALL in southern Chinese children and might be potential biomarkers for pediatric ALL susceptibility and chemotherapeutics.

Project description:Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms.

Dataset Information

IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study.

Publications

IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study.

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