Genetic variations in ATM and H2AX loci contribute to risk of hematological abnormalities in individuals exposed to BTEX chemicals. Issue 4 (2nd March 2022)

• Record Type: Journal Article
• Authors: Jafari Roshan, Samaneh; Mansoori, Yaser; Hosseini, Seyed Reza; Sabour, Davood; Daraei, Abdolreza
• Is Part Of: Journal of clinical laboratory analysis. Volume 36:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-02
• Subjects: ATM‐rs228589 A>T -- BTEXs -- H2AX‐rs7759 A>G -- hematotoxicity -- WRN‐rs1800392 G>T; Diagnosis, Laboratory -- Periodicals; Medical laboratory technology -- Periodicals; 616
• DOI: 10.1002/jcla.24321
• Languages: English
• ISSNs: 0887-8013

Abstract

Abstract: Background: Loci controlling DNA double‐strand breaks (DSBs) repair play an important role in defending against the harmful health effects of benzene, toluene, ethylbenzene, and xylene (BTEX), but their gene variants may alter their repair capacity. The aim of the current study was to determine the relationship of functional polymorphisms ATM‐rs228589 A>T, WRN‐rs1800392 G>T and H2AX‐rs7759 A>G in DBS repair loci with the abnormal hematological indices in workers who exposed to BTEXs. Methods: We included 141 cases with one or more abnormal hematological parameters, who had been occupationally exposed to BTEX chemicals and 152 controls with a similar exposure condition but without any abnormal hematological parameters. Atmospheric concentrations of BTEXs were measured and whole blood samples were taken from the participants to determine hematologic parameters and SNP genotyping. Results: Results showed that T allele of ATM‐rs228589 and G allele of H2AX‐rs7759 had a higher frequency in cases than controls ( p = 0.012 and p = 0.001, respectively). Also, AT and TT genotypes of ATM‐rs228589 and AG and GG genotypes of H2AX‐rs7759 were higher in cases compared to controls. The AT and TT genotypes of ATM‐rs228589 have significant associations with a risk of hematological abnormalities in the codominant (AT vs. AA, p = 0.018), dominant (AT + TT vs. AA, p = 0.010) and overdominant (AT vs. AA + TT, p = 0.037) models. The GG and AG genotypes of H2AX‐rs7759 were in relation with increased risk of abnormal hematological indices under codominant (GA vs. AA, p = 0.009 & GG vs. AA, p = 0.005), dominant (AG + GG vs. AA, p = 0.001), and recessive (GG vs. AA + AG, p = 0.025) models. Conclusions: These observations may help to understand the mechanisms of BTEX hematotoxicity and identify useful biomarkers of risk assessment for workers exposed to BTEX. Abstract : Our results demonstrated that T allele of ATM‐rs228589 and G allele of H2AX‐rs7759 were significantly associated with the risk of BTEX‐related hematotoxicity in an Iranian subpopulation ( p = 0.012 and p = 0.001, respectively). Additionally, we observed an association of reduced RBC counts with the T allele of ATM‐rs228589 ( p ‐trend = 0.010), while increased granulocyte counts and decreased lymphocyte counts were associated with the G allele of H2AX‐rs7759 ( p ‐trend = 0.008 and 0.010, respectively).