Asante-Poku Adwoa, Morgan Portia, Osei-Wusu Stephen, Aboagye Samuel Yaw, Asare Prince, Otchere Isaac Darko, Adadey Samuel Mawuli, Mnika Khuthala, Esoh Kevin, Mawuta Kenneth Hayibor, Arthur Nelly, Forson Audrey, Mazandu Gaston Kuzamunu, Wonkam Ambroise, Yeboah-Manu Dorothy
Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana.
Front Genet. 2022 Feb 15;12:729737. doi: 10.3389/fgene.2021.729737. eCollection 2021.
Despite advancements made toward diagnostics, caused by (Maf) and (Mtbss) remains a major public health issue. Human host factors are key players in (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the gene against both Maf and Mtb infections ( = 0.05; OR = 0.33; 95% CI = 0.32-0.34). A relatively uncommon variant, rs17235409 in the gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04-0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.
尽管在诊断方面取得了进展,但由非洲分枝杆菌(Maf)和结核分枝杆菌塞内加尔株(Mtbss)引起的疾病仍然是一个重大的公共卫生问题。人类宿主因素是结核病(TB)结局和治疗的关键因素。需要开展研究来探究宿主基因组与细菌基因组之间的相互作用。在此,我们在加纳探究了选定的人类/宿主基因组变异与结核病之间的关联。使用多项逻辑回归分析配对的宿主基因型数据和感染细菌分离株信息之间的关联。从191例结核病患者中获取结核分枝杆菌复合群(MTBC)分离株,并通过标准方法将其基因分型为不同的系统发育谱系。235名非疾病参与者用作健康对照。使用TaqMan® SNP基因分型检测法和iPLEX Gold Sequenom Mass基因分型芯片检测了在非洲人群中高频出现的29个与结核病相关基因的单核苷酸多态性(SNP)。在一项关联分析中,我们在326例病例对照样本中使用26个高质量SNP,发现溶质载体家族11成员A1(SLC11A1)基因中的一个保护性变异rs955263,可抵抗Maf和Mtb感染(P = 0.05;比值比[OR] = 0.33;95%置信区间[CI] = 0.32 - 0.34)。在含SH3和富含脯氨酸结构域2(SORBS2)基因中观察到一个相对罕见的变异rs17235409,对Mtb感染具有更强的保护作用(次要等位基因频率[MAF] = 0.06;病例组中次要等位基因频率[PBH] = 0.04;OR = 0.05;95% CI = 0.04 - 0.05)。这些发现表明,SLC11A1和SORBS2是对结核病具有潜在重要保护作用的基因,结核病是西非的一种重要病原体,并强调了在西非开展深入的宿主 - 病原体研究的必要性。