ObjectiveTo explore the single locus mutation that related to hepatitis B virus (HBV) co-infection by means of genome-wide association study (GWAS) in Chinese Han patients with pulmonary tuberculosis (TB).MethodsA total of 946 patients with pulmonary TB enrolled between March 2013 and March 2018 were genotyped by Illumina Human Omni Express gene chip. After quality control, 389 972 single nucleotide polymorphisms (SNPs) of 703 patients with single TB infection and 53 patients with TB-HBV co-infection were included in the follow-up association analysis.ResultsThe SNP with the strongest statistical correlation signal was rs118122819 (P=2.923×10−12, odds ratio=7.933) located on chromosome 8p23.1. Other potential susceptibility genes included CDH4 (rs73309833), MARCH1 (rs3797020), and DNER (rs13393112), etc. In addition, a strong linkage imbalance between rs118122819 and rs4840365 (D’=0.88, r2=0.76) was found, while rs4840365 was located in the MFHAS1 gene region.ConclusionsThis study provides evidence for the presence of susceptibility gene locus for HBV co-infection in pulmonary TB patients, and provides important clues for the mechanism research, disease prevention, and treatment of co-infection. But these associations must be replicated and validated in larger studies.
Objective To explore the relationships between the polymorphisms of inhibitor genes WIF1 and DKK1 in WNT signaling pathway and susceptibility to tuberculosis, clinical characteristics and laboratory indexes. Methods From December 2014 to November 2016, 475 tuberculosis patients and 370 healthy controls of West China Hospital of Sichuan University were enrolled in the study, and the clinical data of the subjects were collected. High-throughput genotyping technique was used to detect the polymorphisms of WIF1 rs58635985 and DKK1 rs11001548 in WNT signaling pathway. The allele frequency distribution, genotype, genetic model, clinical features and laboratory indexes of two single nucleotide polymorphisms were analyzed by χ2 test and logistic regression analysis. Results There was no significant difference in the allele frequency distribution (P=0.275, 0.949), genotype (P=0.214, 0.659) or genetic models: additive model (P=0.214, 0.659), dominant model (P=0.414, 0.827), recessive model (P=0.227, 0.658) of rs58635985 and rs11001548 between the tuberculosis group and the healthy control group. Subgroup analysis showed no significant difference in allele and genotype distribution between rs58635985 and rs11001548 (pulmonary tuberculosis group vs. healthy control group: P>0.05; pulmonary tuberculosis groupvs. extra-pulmonary tuberculosis group: P>0.05). There was no significant difference in the clinical features (fever, night sweat, fatigue,etc.) or laboratory indexes (complete blood count, erythrocyte sedimentation rate, TB-DNA, etc.) (P>0.05). Conclusions There is no association between rs58635985 of WIF1 gene or rs11001548 of DKK1 gene and genetic susceptibility, clinical characteristics and laboratory indexes in Han population in Western China. To expand the sample size for verification and analysis in different populations is necessary.
ObjectiveTo evaluate the expression level and diagnostic value of lnc-PAPSS2-2 (lnc-PA) in peripheral blood of active pulmonary tuberculosis (PTB) patients.MethodsFrom January 2011 to January 2018, 798 patients with active PTB and 1 650 healthy people undergoing health examination in West China Hospital of Sichuan University and their electronic health records (EHR) were collected. Peripheral blood lnc-PA levels were quantified by quantitative real-time polymerase chain reaction method. The data of lnc-PA and EHR were modeled using nomogram, and the receiver operating characteristic (ROC) curves of lnc-PA, EHR and the combination of lnc-PA and EHR were compared to evaluate the diagnostic value of lnc-PA for active PTB.ResultsThe level of lnc-PA was lower in active PTB patients than that in healthy controls (P<0.001). The areas under ROC curve of lnc-PA, EHR and their combination were 0.619, 0.962, and 0.964 in the training set and 0.626, 0.950, and 0.950 in the validation set, respectively.ConclusionThe diagnostic ability of lnc-PA is poor and that of EHR is good, which indicates that the clinical value of lnc-PA as a biomarker of active PTB remains to be further explored.
ObjectiveTo explore the relationship between hexokinase domain-containing protein 1 (HKDC-1) single nucleotide polymorphism (SNP) and first-line anti-tuberculosis drug-induced liver injury (ATDILI) in tuberculosis patients in western China.MethodsFrom November 2016 to April 2018, 746 tuberculosis patients treated in West China Hospital of Sichuan University were collected and divided into ATDILI group and non-ATDILI group according to the liver function indicators. DNA was extracted by QIAamp® DNA Blood Mini Kit (Qiagen, Germany). Seven SNPs of the HKDC-1 gene were genotyped by high-throughput genotyping technique and the differences between the two groups were compared.ResultsThere were 118 ATDILI and 628 non-ATDILI cases enrolled in this study. In clinical symptoms, the differences in incidences of fever and weight loss between the two groups were statistically significant (P=0.004, 0.024). The C allele at rs906219 was associated with low susceptibility to ATDILI [odds ratio (OR)=0.737, 95% confidence interval (CI) (0.556, 0.957), P=0.033], and the additive model and dominant model showed that CC/CA genotype had a lower risk of ATDILI than AA genotype [CC vs. AA: OR=0.563, 95%CI (0.325, 0.976), P=0.039; CC+CA vs. AA: OR=0.533, 95%CI (0.348, 0.817), P=0.004].ConclusionThe SNP of rs906219 in HKDC-1 is correlated with ATDILI occurrence in tuberculosis patients in western China, which provides clues for personalized anti-tuberculosis treatment.