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  • Title: Genetic Variation of Costimulatory Molecules, Including Cytotoxic T-Lymphocyte Antigen 4, Inducible T-Cell Costimulator, Cluster Differentiation 28, and Programmed Cell Death 1 Genes, in Iranian Patients With Leukemia.
    Author: Ramzi M, Arandi N, Saadi MI, Yaghobi R, Geramizadeh B.
    Journal: Exp Clin Transplant; 2020 Nov; 18(6):719-724. PubMed ID: 29697355.
    Abstract:
    OBJECTIVES: There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma. MATERIALS AND METHODS: This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.3 A/G, 1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (17 C/T), were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Our results showed that the TT genotype and T allele of the CTLA-4 -318 T/C polymorphism, the AA genotype of CTLA-4 +49 A/G polymorphism, and the CT genotype of PD-1 1.9 C/T polymorphism were significantly higher in healthy controls (P < .05). However, the AG genotype of the CTLA-4 +49 A/G, the CC genotype of the PD-1 1.9 C/T, and the CT genotype of the CD28 +17C/T polymorphism were significantly increased in patients with leukemia (P < .05). When the genotype frequency of costimulatory genes was compared between different leukemia groups, we observed that the A allele of the CTLA-4 +49 A/G and the CC genotype and C allele of the CD28 +17 C/T polymorphism were significantly higher in patients with acute leukemia than in those with chronic leukemia (P < .05). Among leukemia patients, the AA genotype of CTLA-4 +49A/G polymorphism was significantly increased in patients with acute myeloid leukemia, whereas the AG genotype was more prevalent in patients with acute lymphoblastic leukemia (P < .05). CONCLUSIONS: We show for the first time that genetic variations of costimulatory molecules CTLA-4, CD28, and PD-1 may be associated with susceptibility of Iranian patients to leukemia.
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