Ahmadi Iraj, Anvari Enayat, Bastaminejad Saiyad, Sakhaee Fatemeh, Ghazanfari Jajin Morteza, Fateh Abolfazl
Department of Physiology, School of Medicine, Ilam University of Medical Science, Ilam, Iran.
Department of Genetics and Molecular Medicine, School of ParaMedicine, Ilam University of Medical Sciences, Ilam, Iran.
Sci Rep. 2025 Sep 1;15(1):32127. doi: 10.1038/s41598-025-18112-9.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of infectious disease mortality globally. Host genetic factors, particularly those involved in innate immunity like Cluster of Differentiation 14 (CD14), may influence susceptibility to TB. This study investigated the association of two CD14 promoter polymorphisms, rs2569190 (C-159 T) and rs2569191 (A-1145G), with TB susceptibility in the Kurdish population of Iran. A prospective case-control study was conducted, enrolling 303 newly diagnosed TB patients (280 drug-sensitive, 23 MDR-TB) and 288 age- and sex-matched healthy Kurdish controls from Ilam, Iran. Genotyping for rs2569190 and rs2569191 was performed using PCR-RFLP. The TT genotype of rs2569190 and the GG genotype of rs2569191 were significantly more frequent in both drug-sensitive and MDR-TB patient groups compared to controls (P < 0.05). Under the codominant model, the TT genotype of rs2569190 (OR = 1.68, 95% CI 1.15-2.45) and the GG genotype of rs2569191 (OR = 1.55, 95% CI 1.06-2.26) were associated with increased TB susceptibility. Haplotype analysis revealed a higher prevalence of the CG haplotype in TB patients and an association of the TG haplotype with increased TB risk. In conclusions, this study suggests that the CD14 promoter polymorphisms rs2569190 and rs2569191 are associated with increased susceptibility to tuberculosis in the Kurdish population of Iran. These findings highlight the potential role of CD14 genetic variations in TB pathogenesis and warrant further investigation in other populations and functional studies to elucidate the underlying mechanisms.
由结核分枝杆菌（Mtb）引起的结核病（TB）仍然是全球传染病死亡的主要原因。宿主遗传因素，特别是那些参与固有免疫的因素，如分化簇14（CD14），可能会影响对结核病的易感性。本研究调查了伊朗库尔德人群中CD14启动子的两个多态性rs2569190（C-159T）和rs2569191（A-1145G）与结核病易感性的关联。进行了一项前瞻性病例对照研究，招募了303名新诊断的结核病患者（280名药物敏感患者，23名耐多药结核病患者）以及来自伊朗伊拉姆的288名年龄和性别匹配的健康库尔德对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对rs2569190和rs2569191进行基因分型。与对照组相比，rs2569190的TT基因型和rs2569191的GG基因型在药物敏感和耐多药结核病患者组中均明显更为常见（P < 0.05）。在共显性模型下，rs2569190的TT基因型（比值比[OR] = 1.68，95%置信区间[CI] 1.15 - 2.45）和rs2569191的GG基因型（OR = 1.55，95% CI 1.06 - 2.26）与结核病易感性增加相关。单倍型分析显示，结核病患者中CG单倍型的患病率较高，且TG单倍型与结核病风险增加相关。总之，本研究表明CD14启动子多态性rs2569190和rs2569191与伊朗库尔德人群中结核病易感性增加相关。这些发现突出了CD14基因变异在结核病发病机制中的潜在作用，值得在其他人群中进一步研究以及开展功能研究以阐明潜在机制。
