Liang Li, Zhang Qing, Luo Liu-Lin, Yue Jun, Zhao Yan-Lin, Han Min, Liu Li-Rong, Xiao He-Ping
Shanghai Key Laboratory of Mycobacterium Tuberculosis, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, Shanghai, PR China.
Shanghai Key Laboratory of Mycobacterium Tuberculosis, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, Shanghai, PR China.
Infect Genet Evol. 2016 Dec;46:23-27. doi: 10.1016/j.meegid.2016.10.016. Epub 2016 Oct 22.
Prostaglandin E2 (PGE2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. PGE2 modulates a variety of immune functions via four receptors (EP1-EP4), which mediate distinct PGE2 effects. Mice lacking EP2 are more susceptible to infection by Mycobacterium tuberculosis (M.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. Our aim was to assess whether single nucleotide polymorphisms (SNPs) in EP2 increase the risk of tuberculosis.
DNA re-sequencing revealed five common EP2 variants in the Chinese Han population. We sequenced the EP2 gene from 600 patients and 572 healthy controls to measure SNP frequencies in association with tuberculosis infections (TB) within the population.
The rs937337 polymorphism is associated with increased risk to tuberculosis (p=0.0044, odds ratio [OR], 1.67; 95% confidential interval,1.22-2.27). The rs937337 AA genotype and the rs1042618 CC genotype were significantly associated with TB. An estimation of the frequencies of haplotypes revealed a single protective haplotype GACGC for tuberculosis (p=0.00096, odds ratio [OR], 0.56; 95% confidential interval, 0.41-0.77). Furthermore, we determined that the remaining SNPs of EP2 were nominally associated with clinical patterns of disease.
We identified genetic polymorphisms in EP2 associated with susceptibility to tuberculosis within a Chinese population. Our data support that EP2 SNPs are genetic predispositions of increased susceptibility to TB and to different clinical patterns of disease.
前列腺素E2（PGE2）是急性和慢性感染期间炎症免疫反应的重要脂质介质。PGE2通过四种受体（EP1 - EP4）调节多种免疫功能，这些受体介导不同的PGE2效应。缺乏EP2的小鼠更易受到结核分枝杆菌（M.tb）感染，细菌载量更高，肉芽肿病变的大小和数量增加。我们的目的是评估EP2中的单核苷酸多态性（SNP）是否会增加患结核病的风险。
DNA重测序揭示了中国汉族人群中五个常见的EP2变体。我们对600例患者和572名健康对照的EP2基因进行测序，以测量人群中与结核感染（TB）相关的SNP频率。
rs937337多态性与患结核病风险增加相关（p = 0.0044，优势比[OR]，1.67；95%置信区间，1.22 - 2.27）。rs937337 AA基因型和rs1042618 CC基因型与结核病显著相关。单倍型频率估计显示存在一种针对结核病的保护性单倍型GACGC（p = 0.00096，优势比[OR]，0.56；95%置信区间，0.41 - 0.77）。此外，我们确定EP2的其余SNP与疾病的临床模式存在名义上的关联。
我们在中国人群中鉴定出与结核病易感性相关的EP2基因多态性。我们的数据支持EP2 SNP是结核病易感性增加以及不同疾病临床模式的遗传易感性因素。
