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白细胞介素-10、白细胞介素-12p40和白细胞介素-13基因中的单核苷酸多态性与胶质瘤易感性

Single Nucleotide Polymorphisms in IL-10, IL-12p40, and IL-13 Genes and Susceptibility to Glioma.

作者信息

Shamran Haidar A, Ghazi Haidar F, Al-Salman Ahmed, Al-Juboory Ahmad A, Taub Dennis D, Price Robert L, Nagarkatti Mitzi, Nagarkatti Prakash S, Singh Udai P

机构信息

1. Medical research Unit, Microbiology Department, School of Medicine, University of AL-Nahrain, Baghdad Iraq.

2. Biotechnology Department, School of Science, University of Baghdad.

出版信息

Int J Med Sci. 2015 Sep 19;12(10):790-6. doi: 10.7150/ijms.12609. eCollection 2015.

Abstract

Glioma is one of the most aggressive and most common tumors of the central nervous system (CNS) in humans. The exact causes of glioma are not well known, but evidence suggests the involvement of genetic factors in addition to environmental risk factors. The present study aimed to determine whether polymorphisms in IL-10-1082A/G, IL-12p40 1188C/A, and IL-13+2044G/A (rs20541) are associated with the incidence of glioma in Iraqi patients. Ninety-six patients with different grades of glioma and 40 apparently healthy individuals were recruited. A blood sample and genomic DNA were collected from all subjects. The amplification refractory mutation system and sequence-specific primer polymerase chain reaction (PCR) were used for genotyping of IL-10-1082A/G and IL-12p40 1188C/A, respectively; whereas, the IL-13+2044G/A was detected by DNA sequencing after amplification of the genes by PCR. All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in patients and controls. In IL-10-1082A/G, these genotypes frequencies were AA (75%), AG (22.93%) and GG (2.07%) in patients as compared to similar frequencies (62.5%), (27.5%) and (10%) respectively, in controls. The variant IL-12p40 1188C/A genotype was AA (72.92%), AC (23.96%), and CC (3.13%%) in patients as compared to 65%, 30%, and 5%, respectively, in controls. The frequencies of IL-13+2044G/A genotypes (GG, GA, and AA) were 89.58%, 9.37%, and 1.04% among patients versus 47.5%, 32.5% and 20%, respectively, among controls. These results suggest a protective role of mutant alleles G and A in IL-10-1082A/G and IL-13+2044G/A against gliomas. Further studies with more rigorous parameter designs will be needed to confirm the current findings.

摘要

神经胶质瘤是人类中枢神经系统(CNS)中最具侵袭性且最常见的肿瘤之一。神经胶质瘤的确切病因尚不清楚,但有证据表明除环境风险因素外,遗传因素也与之相关。本研究旨在确定白细胞介素10(IL-10)-1082A/G、白细胞介素12p40 1188C/A以及白细胞介素13 +2044G/A(rs20541)基因多态性是否与伊拉克患者神经胶质瘤的发病率相关。招募了96例不同级别的神经胶质瘤患者和40名明显健康的个体。采集了所有受试者的血样和基因组DNA。分别采用扩增阻滞突变系统和序列特异性引物聚合酶链反应(PCR)对IL-10-1082A/G和IL-12p40 1188C/A进行基因分型;而IL-13 +2044G/A则通过PCR扩增基因后进行DNA测序检测。所有单核苷酸多态性(SNP)均处于哈迪-温伯格平衡,且在患者和对照组中均呈现三种基因型。在IL-10-1082A/G中,患者的这些基因型频率分别为AA(75%)、AG(22.93%)和GG(2.07%),而对照组的相似频率分别为(62.5%)、(27.5%)和(10%)。变异型IL-12p40 1188C/A基因型在患者中为AA(72.92%)、AC(23.96%)和CC(3.13%),而在对照组中分别为65%、30%和5%。IL-13 +2044G/A基因型(GG、GA和AA)在患者中的频率分别为89.58%、9.37%和1.04%,而在对照组中的频率分别为47.5%、32.5%和20%。这些结果表明,IL-10-1082A/G和IL- +2044G/A中的突变等位基因G和A对神经胶质瘤具有保护作用。需要进一步进行参数设计更严谨的研究来证实当前的发现。

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