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巴西亚马逊地区一个混合人群中,、和基因的变异对急性淋巴细胞白血病易感性的影响。

Influence of variants of the , , and genes on susceptibility to acute lymphoblastic leukemia in an admixed population from the brazilian amazon.

作者信息

de Souza Tatiane Piedade, de Carvalho Darlen Cardoso, Wanderley Alayde Viera, Fernandes Sweny Marinho, Rodrigues Juliana Carla Gomes, Cohen-Paes Amanda, Fernandes Marianne Rodrigues, Mello Junior Fernando Augusto Rodrigues, Pastana Lucas Favacho, Vinagre Lui Wallacy Morikawa Souza, Silva Artur Luiz da Costa, de Assumpção Paulo Pimentel, Santos Sidney, Khayat André Salim, Dos Santos Ney Pereira Carneiro

机构信息

Laboratory of Human and Medical Genetics, Institute of Biological Sciences Belém, Pará, PA, Brazil.

Research Center of Oncology, Federal University of Pará Belém, Pará, PA, Brazil.

出版信息

Am J Transl Res. 2020 Dec 15;12(12):8216-8224. eCollection 2020.

Abstract

Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in children. Polymorphisms that alter the normal function of the microRNAs involved in the development of ALL have been widely investigated, although published data on these polymorphisms in admixed populations are scarce. We investigated the role of 10 polymorphisms in the microRNA and protein-coding genes of the microRNA synthesis complex in susceptibility to pediatric B-cell ALL. The study includes 100 pediatric ALL patients and 180 healthy individuals. The statistical analyses were run in SPSS v.25.0. In the case of the microRNA synthesizing genes, a significant pattern was found in only gene, that is, the rs3805500 polymorphism of , in which the homozygous mutant (AA) genotype was associated with a threefold increase in the risk of developing ALL when compared to other genotypes (P=0.004, OR=2.913, CI=1.415-5.998). In the microRNA coding genes, the homozygous mutant rs3746444 genotype of the gene was associated with a 17-fold increase in the risk of development of ALL (P<0.001, OR=17.797, CI=5.55-57.016). A protective effect against the development of ALL was also observed in the carriers of the wild homozygous rs2505901 genotype in the gene. Our findings highlight the potential of these polymorphisms in the genes involving in the coding of microRNAs for the evaluation of the risk of contracting ALL in the population of the Brazilian Amazon region. These findings contribute to a more complete understanding of the complex etiology of ALL.

摘要

急性淋巴细胞白血病(ALL)是儿童中最常见的癌症类型。尽管关于混合人群中这些多态性的已发表数据很少,但改变参与ALL发生发展的微小RNA正常功能的多态性已得到广泛研究。我们研究了微小RNA合成复合物的微小RNA和蛋白质编码基因中的10种多态性在儿童B细胞ALL易感性中的作用。该研究包括100名儿童ALL患者和180名健康个体。统计分析在SPSS v.25.0中进行。在微小RNA合成基因方面,仅在一个基因中发现了显著模式,即基因的rs3805500多态性,其中纯合突变体(AA)基因型与发生ALL的风险相比其他基因型增加了两倍(P = 0.004,OR = 2.913,CI = 1.415 - 5.998)。在微小RNA编码基因中,基因的纯合突变体rs3746444基因型与发生ALL的风险增加了16倍相关(P < 0.001,OR = 17.797,CI = 5.55 - 57.016)。在基因的野生纯合rs2505901基因型携带者中也观察到对ALL发生的保护作用。我们的研究结果突出了这些涉及微小RNA编码的基因中的多态性在评估巴西亚马逊地区人群患ALL风险方面的潜力。这些发现有助于更全面地理解ALL复杂的病因。

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