Etokebe G E, Bulat-Kardum L, Johansen M S, Knezevic J, Balen S, Matakovic-Mileusnic N, Matanic D, Flego V, Pavelic J, Beg-Zec Z, Dembic Z
Immunology Laboratory, Department of Oral Biology, University of Oslo, Oslo, Norway.
Scand J Immunol. 2006 Feb;63(2):136-41. doi: 10.1111/j.1365-3083.2005.01716.x.
Genetic susceptibility to tuberculosis includes several unknown yet different loci each contributing to a small extent. Intronic polymorphisms within the interferon-gamma (IFN-gamma) gene IFNG T+874A and IFNG G+2109A correlate with the IFN-gamma production in vitro, and the frequency of potential high IFN-gamma producers was previously reported by others to be lower in patients than in controls from Sicily. The aim of this study was to determine whether there is an association between polymorphisms in the IFN-gamma gene and predisposition to tuberculosis. We analysed two IFNG SNPs (T+874A and G+2109A) in patients (n = 253) hospitalized in Rijeka (Croatia) and controls (n = 519) from the same area. One-fifth of the controls were healthy contacts of the diseased, and the rest were blood donors. IFNG alleles, their predicted haplotypes or genotypes were not associated with disease susceptibility. Thus, we could not reproduce results from Sicilian case-control study. However, T/T+874 (possible high IFN-gamma producer) and +874A/A (putative low producer) genotypes were associated with microscopically positive-negative forms of disease. Haplotypes (T+874A and G+2109A) based on a prediction by software phase and subsequent genotype analysis corroborated these findings. Patients had significantly higher frequency of genotypes without T at +874 (AA/AA; AA/AG and AG/AG) in microscopy- or bacterial culture-positive groups compared with their negative counterparts. These data suggest an association with disease severity rather than susceptibility to tuberculosis in Croatian Caucasian population.
结核病的遗传易感性包括几个尚不明确但各不相同的基因座，每个基因座的作用都较小。干扰素-γ（IFN-γ）基因IFNG T+874A和IFNG G+2109A内的内含子多态性与体外IFN-γ的产生相关，此前有其他人报道，西西里岛患者中潜在高IFN-γ产生者的频率低于对照组。本研究的目的是确定IFN-γ基因多态性与结核病易感性之间是否存在关联。我们分析了里耶卡（克罗地亚）住院患者（n = 253）和来自同一地区的对照组（n = 519）中的两个IFNG单核苷酸多态性（T+874A和G+2109A）。五分之一的对照组是患病者的健康接触者，其余为献血者。IFNG等位基因、其预测的单倍型或基因型与疾病易感性无关。因此，我们无法重现西西里岛病例对照研究的结果。然而，T/T+874（可能的高IFN-γ产生者）和+874A/A（假定的低产生者）基因型与疾病的显微镜下阳性-阴性形式相关。基于软件分型预测及后续基因型分析的单倍型（T+874A和G+2109A）证实了这些发现。与显微镜或细菌培养阴性组相比，显微镜或细菌培养阳性组患者中+874位点无T的基因型（AA/AA；AA/AG和AG/AG）频率显著更高。这些数据表明，在克罗地亚白种人群中，这与疾病严重程度相关，而非与结核病易感性相关。
