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沙特皮肤利什曼病患者中TNF-α - 308 G/A和IFN-γ + 874 A/T基因多态性

TNF-α - 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis.

作者信息

Ahmed Ahmed A, Rasheed Zafar, Salem Tarek, Al-Dhubaibi Mohammed S, Al Robaee Ahmad A, Alzolibani Abdullateef A

机构信息

Research Center, College of Medicine, Qassim University, Buraidah, Saudi Arabia.

Department of Medical Biochemistry, College of Medicine, Qassim University, P.O. Box 6655, Buraidah, KSA, 51452, Saudi Arabia.

出版信息

BMC Med Genet. 2020 May 13;21(1):104. doi: 10.1186/s12881-020-01043-9.

Abstract

BACKGROUND

Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α - 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia.

METHODS

This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α - 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR.

RESULTS

Evaluation of genotyping and allelic frequency of TNF-α - 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α - 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p < 0.05). Furthermore, a strong association was observed between the susceptibility of L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles.

CONCLUSIONS

This is the first report that shows the gene polymorphisms of TNF-α - 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection.

摘要

背景

皮肤利什曼病(CL)与免疫遗传因素密切相关。本研究旨在检测沙特阿拉伯中部地区CL患者中TNF-α -308和IFN-γ +874基因多态性与利什曼原虫(L)种易感性之间的关联。

方法

这是一项病例对照研究,涉及169名感染不同L.种的沙特受试者和199名来自沙特阿拉伯中部地区的健康对照。使用聚合酶链反应(PCR)对所有受试者进行TNF-α -308 G/A和IFN-γ +874 A/T基因多态性分析。

结果

不同L.种中TNF-α -308 G/A的基因分型和等位基因频率评估显示,与对照组相比无显著关联(p>0.05)。但热带利什曼原虫病例中,TNF-α -308 A等位基因频率显著高于G等位基因频率(p = 0.0004)。IFN-γ +874(TT与AA + AT隐性)的基因分型评估以及IFN-γ +874(T与A)的等位基因频率评估显示,与健康对照组相比,硕大利什曼原虫及所有CL病例中的频率显著更高(p<0.05)。此外,在硕大利什曼原虫、热带利什曼原虫或所有CL病例的易感性与协同组合的高TNF-α 308/INF-γ 874等位基因之间观察到强关联。

结论

这是首次报道沙特不同L.种感染患者中TNF-α -308 G/A和IFN-γ +874 A/T基因多态性。数据表明,TNF-α -308 G/A基因多态性与沙特受试者CL易感性无关。仅在热带利什曼原虫的A与G等位基因频率之间发现相关性。重要的是,发现IFN-γ +874 A/T多态性与硕大利什曼原虫易感性以及所有CL受试者相关。此外,协同组合的高TNF-α 308/INF-γ 874等位基因的数据强烈表明它们在利什曼原虫感染易感性中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4696/7218653/4439244676e1/12881_2020_1043_Fig1_HTML.jpg

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