Genetic evidence for predisposition to acute leukemias due to a missense mutation (p.Ser518Arg) in ZAP70 kinase: a case-control study.

Autor: Khashei Varnamkhasti K; Department of Medical Laboratory Sciences, Faculty of Medicine, Kazerun branch, Islamic Azad University, Kazerun, Iran., Khashei Varnamkhasti S; Department of Medical Laboratory Sciences, Faculty of Medicine, Kazerun branch, Islamic Azad University, Kazerun, Iran., Shahrouzian A; Department of Genetics, College of Science, Kazerun branch, Islamic Azad University, Kazerun, Iran., Rahimzadeh M; Department of Genetics, College of Science, Kazerun branch, Islamic Azad University, Kazerun, Iran., Naeimi L; Department of Genetics, College of Science, Kazerun branch, Islamic Azad University, Kazerun, Iran., Naeimi B; Department of Medical Laboratory Sciences, Fucalty of Paramedical, Bushehr University of Medical Sciences, Bushehr, Iran., Naeimi S; Department of Biology, Zand Institute of Higher Education, Shiraz, Iran. si.naeimi@iau.ac.ir.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2024 Aug 07; Vol. 17 (1), pp. 200. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1186/s12920-024-01961-0
Abstrakt: Background: The apparent lack of additional missense mutations data on mixed-phenotype leukemia is noteworthy. Single amino acid substitution by these non-synonymous single nucleotide variations can be related to many pathological conditions and may influence susceptibility to disease. This case-control study aimed to unravel whether the ZAP70 missense variant (rs104893674 (C > A)) underpinning mixed-phenotype leukemia.
Methods: The rs104893674 was genotyped in clients who were mixed-phenotype acute leukemia-, acute lymphoblastic leukemia- and acute myeloid leukemia-positive and matched healthy controls, which have been referred to all major urban hospitals from multiple provinces of country- wide, IRAN, from February 11' 2019 to June 10' 2023, by amplification refractory mutation system-polymerase chain reaction method. Direct sequencing for rs104893674 of the ZAP70 gene was performed in a 3130 Genetic Analyzer.
Results: We found that the AC genotype of individuals with A allele at this polymorphic site (heterozygous variant-type) contribute to the genetic susceptibility to acute leukemia of both forms, acute myeloid leukemia and acute lymphoblastic leukemia as well as with a mixed phenotype. In other words, the ZAP70 missense variant (rs104893674 (C > A)) increases susceptibility of distinct cell populations of different (myeloid and lymphoid) lineages to exhibiting cancer phenotype. The results were all consistent with genotype data obtained using a direct DNA sequencing technique.
Conclusion: Of special interest are pathogenic missense mutations, since they generate variants that cause specific molecular phenotypes through protein destabilization. Overall, we discovered that the rs104893674 (C > A) variant chance in causing mixed-phenotype leukemia is relatively high.
(© 2024. The Author(s).)
Databáze: MEDLINE
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