Chao Zhou1, Nan Ouyang2, Qing Hui Li3, Su Xin Luo4, Quan He5, Han Lei6, Qing Liu7. 1. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: zhouchao2008@hotmail.com. 2. Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: shenhuxi107@163.com. 3. Department of Cardiology, The People's Hospital of Ningxia, Ningxia, PR China. Electronic address: 18995167196@189.com. 4. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: luosuxin0204@163.com. 5. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: hequan822@aliyun.com. 6. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: xiaoban@cqmu.edu.cn. 7. Centre for Clinical Research, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: qingliu5566@aliyun.com.
Abstract
BACKGROUND: Interleukin (IL) -18 is crucial to host defense against mycobacterial infections. Recent studies have indicated IL-18 gene polymorphisms are associated with susceptibility to several clinical diseases. OBJECTIVE: The aim of this study is to investigate the association of IL-18 (-137G/C and -607C/A) gene promoter single nucleotide polymorphisms (SNPs) with susceptibility to tuberculosis (TB), and the effects of those SNPs to its protein producing capacity in Chinese Han population. METHODS: 407 TB patients (including 113 children and 294 adults) and 469 healthy volunteers (including 167 children and 302 adults) from Chinese Han population were enrolled. The IL-18 gene promoter polymorphisms at positions of -137 and -607 were determined by sequence specific primer-polymerase chain reaction (SSP-PCR). The IL-18 levels in the supernatants of PBMCs from 46 healthy volunteers were measured by ELISA. RESULTS: The gene distribution of IL-18 -137G/C and -607C/A showed none difference between adult and pediatric population. The frequency of IL-18 -137GG genotype was significantly higher in total TB group than that in total healthy control group (79.1% V 69.3%, P<0.01), while the frequencies of GC genotype and C allele were conversely lower (19.2% V 27.9%, P<0.01; 11.3% V 16.7%, P<0.01 respectively). The difference of the -137CC genotype distribution between patients and controls was not observed. At the -607C/A polymorphic site, patient and control groups had a very similar gene distribution. Isolated PBMCs with IL-18 -137GC/CC genotype were able to produce a higher level of IL-18 than those with IL-18 -137GG genotype, either spontaneously or in response to PMA plus calcimycin A23187. CONCLUSION: IL-18 -137G/C polymorphism contributed to TB susceptibility in Chinese Han population. Allele G might be a predisposing gene of TB, while allele C probably plays a role in preventing mycobacterium tuberculosis infection by promoting more vigorous protein expression.
BACKGROUND:Interleukin (IL) -18 is crucial to host defense against mycobacterial infections. Recent studies have indicated IL-18 gene polymorphisms are associated with susceptibility to several clinical diseases. OBJECTIVE: The aim of this study is to investigate the association of IL-18 (-137G/C and -607C/A) gene promoter single nucleotide polymorphisms (SNPs) with susceptibility to tuberculosis (TB), and the effects of those SNPs to its protein producing capacity in Chinese Han population. METHODS: 407 TB patients (including 113 children and 294 adults) and 469 healthy volunteers (including 167 children and 302 adults) from Chinese Han population were enrolled. The IL-18 gene promoter polymorphisms at positions of -137 and -607 were determined by sequence specific primer-polymerase chain reaction (SSP-PCR). The IL-18 levels in the supernatants of PBMCs from 46 healthy volunteers were measured by ELISA. RESULTS: The gene distribution of IL-18-137G/C and -607C/A showed none difference between adult and pediatric population. The frequency of IL-18 -137GG genotype was significantly higher in total TB group than that in total healthy control group (79.1% V 69.3%, P<0.01), while the frequencies of GC genotype and C allele were conversely lower (19.2% V 27.9%, P<0.01; 11.3% V 16.7%, P<0.01 respectively). The difference of the -137CC genotype distribution between patients and controls was not observed. At the -607C/A polymorphic site, patient and control groups had a very similar gene distribution. Isolated PBMCs with IL-18 -137GC/CC genotype were able to produce a higher level of IL-18 than those with IL-18 -137GG genotype, either spontaneously or in response to PMA plus calcimycin A23187. CONCLUSION:IL-18-137G/C polymorphism contributed to TB susceptibility in Chinese Han population. Allele G might be a predisposing gene of TB, while allele C probably plays a role in preventing mycobacterium tuberculosis infection by promoting more vigorous protein expression.
Authors: Noha A Hassuna; Mohamed El Feky; Aliae A R Mohamed Hussein; Manal A Mahmoud; Naglaa K Idriss; Sayed F Abdelwahab; Maggie A Ibrahim Journal: PLoS One Date: 2021-01-07 Impact factor: 3.240