Mabunda Nédio, Alvarado-Arnez Lucia Elena, Vubil Adolfo, Mariamo Amina, Pacheco Antonio G, Jani Ilesh V, Moraes Milton O
Laboratório de Virologia Molecular, Instituto Nacional de Saúde, PO Box 264, Maputo, Mozambique.
Mol Biol Rep. 2015 Jan;42(1):71-6. doi: 10.1007/s11033-014-3741-1. Epub 2014 Sep 20.
Several host and environmental factors contribute to tuberculosis outcome, interestingly single nucleotide polymorphisms (SNPs) in candidate genes have been evaluated in populations with different ethnicities and TB infection. In the present study we focused on SNPs in cytokine and inflammatory mediator genes: tumor necrosis factor (TNF) -308G>A (rs1800629), interleukin-10 (IL10) -819C>T (rs1800871), interferon-gamma (IFNG) +874T>A (rs2430561), and leukotriene A4 hydrolase (LTA4H) rs1978331, rs17525495 and rs2660898 in a case-control study involving 102 pulmonary tuberculosis patients and 456 controls from Mozambique. LTA4H, IL10 and IFNG SNPs showed no associations with pulmonary tuberculosis. However, distribution of the TNF -308A allele, genotype and carrier frequencies showed a significant risk association with tuberculosis that was maintained after adjustment for non-genetic variables and Bonferroni correction (AA genotype, OR = 1.9, p Bonf < 0.001; A allele OR = 2.9, p Bonf = 0.005 and GA/AA carrier OR = 2.6, p Bonf = 0.035). Interestingly, this association has not been reported in a sub-Saharan African population before. Our results suggest a role of -308 TNF polymorphism and tuberculosis susceptibility.
多种宿主和环境因素会影响结核病的转归,有趣的是,人们已在不同种族和结核感染人群中评估了候选基因中的单核苷酸多态性(SNP)。在本研究中,我们聚焦于细胞因子和炎症介质基因中的SNP:肿瘤坏死因子(TNF)-308G>A(rs1800629)、白细胞介素-10(IL10)-819C>T(rs1800871)、干扰素-γ(IFNG)+874T>A(rs2430561),以及白三烯A4水解酶(LTA4H)的rs1978331、rs17525495和rs2660898。我们进行了一项病例对照研究,涉及102例来自莫桑比克的肺结核患者和456名对照。结果显示,LTA4H、IL10和IFNG的SNP与肺结核无关联。然而,TNF -308A等位基因、基因型及携带者频率的分布显示出与结核病存在显著的风险关联,在对非遗传变量进行校正并经Bonferroni校正后,该关联依然存在(AA基因型,OR = 1.9,p Bonf < 0.001;A等位基因,OR = 2.9,p Bonf = 0.005;GA/AA携带者,OR = 2.6,p Bonf = 0.035)。有趣的是,此前在撒哈拉以南非洲人群中尚未报道过这种关联。我们的结果提示了-308 TNF多态性与结核病易感性之间的关系。