ObjectiveTo explore the relationship between the single nucleotide polymorphisms of interleukin (IL)-23R gene and susceptibility to pulmonary tuberculosis in Southwest Chinese Han population.MethodsA total of 680 pulmonary tuberculosis patients (pulmonary tuberculosis group) and 680 healthy controls (healthy control group) diagnosed or examined between January 2014 and February 2016 were recruited from West China Hospital, Sichuan University. Improved multiplex ligation detection reaction (iMLDR) method was used to detect the polymorphism of rs1495965, rs7518660, rs7532161, rs10889677 and rs11465802 of IL-23R gene. The differences in allele frequency distribution, genotype, and genetic model of these five loci between pulmonary tuberculosis patients and healthy control were conducted by using SPSS20.0 and PLINK 1.07. Linkage disequilibrium and haplotype analysis were also carried out by Haploview 4.2.ResultsFinally, 657 pulmonary tuberculosis patients and 669 healthy controls were enrolled for further analyzed. The difference in the allele frequency distribution A (P=0.048), AA genotype (P=0.048) and additive model AA/GG (P=0.048) in rs1495965 was significant between the pulmonary tuberculosis group and healthy control group when we adjusted the gender and age. However, after correction by Bonferroni, the differences in allele frequency distribution, genotype and additive model of all these five loci between the two groups were not statistically significant (P>0.05). rs7518660, rs10889677 and rs11465802 had strong linkage disequilibrium (LD) with each other (r2>0.80); however, there was no association between haplotype GCA and tuberculosis susceptibility (P=0.343).ConclusionsThere is no association between rs1495965, rs7518660, rs7532161, rs10889677 and rs11465802 of IL-23R gene and genetic pulmonary tuberculosis susceptibility in Southwest Chinese Han population. To add loci in the coding region and analysis in different populations is necessary.
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 single nucleotide polymorphisms (SNPs) of the Toll-like receptor 4 (TLR4) gene and the risk of pulmonary tuberculosis (PTB) more comprehensively and objectively through meta-analysis.MethodsWe searched all available articles published before June 13th, 2019 in main Chinese and English databases systematically and comprehensively, including PubMed, Embase, China National Knowledge Infrastructure, Wanfang and CQVIP databases. The literature was screened according to the inclusion and exclusion criteria set in advance. In addition, the basic characteristics and data of the included literature were recorded according to a pre-made data collection form. Statistical analyses were performed using the Stata 15.0 software.ResultsA total of 17 eligible original articles were included in the study eventually. Furthermore, allele and genotype data of the 4 most widely studied SNPs (rs4986790, rs4986791, rs10759932, and rs11536889) in the TLR4 gene were extracted. And their allelic model, dominant model, recessive model, homozygous model, and heterozygous model were separately analyzed by meta-analysis. The results showed that the C allele of rs10759932 increased the risk of PTB [odd ratio (OR)=1.144, 95% confidence interval (CI) (1.043, 1.254), P=0.004]. Compared with the TT genotype, the CC+CT genotype and the CT genotype alone of rs10759932 also increased the risk of PTB [OR=1.218, 95%CI (1.084, 1.369), P=0.001; OR=1.227, 95%CI (1.085, 1.387), P=0.001]. Nevertheless, there was no statistical correlation between the other three SNPs (rs4986790, rs4986791 and rs11536889) and the susceptibility to PTB (P>0.05).ConclusionThe allele model, dominant model (CC+CT vs. TT), and heterozygous model (CT vs. TT) of rs10759932 located on the TLR4 gene are closely related to the risk of PTB.
Objective To analyze the human leukocyte antigen (HLA) gene polymorphism and haplotype frequency and distribution in Han patients with end stage renal disease (ESRD) in Sichuan province, and explore the correlation of HLA gene polymorphism and haplotype with the susceptibility to ESRD in Sichuan Han patients. Methods Polymerase chain reaction-sequence specific oligonucleotide probe hybridization typing technique was used to detect the HLA-A, -B, -DRB1, and -DQB1 genotypes of Han patients with ESRD and healthy participants. The allele and haplotype frequencies in the ESRD group and the control group were analyzed using SPSS 25.0 and Arlequin 3.5.2.2 softwares. Results A total of 756 ESRD patients and 1118 healthy participants were enrolled. In the four loci of HLA-A, -B, -DRB1, and -DQB1, the frequency of HLA-B*39 allele in the ESRD group was higher than that in the control group [3.37% vs. 2.19%; χ2=4.850, P=0.028, odds ratio (OR)=1.558, 95% confidence interval (CI) (1.047, 2.319)], the frequency of HLA-DQB1*06 allele in the ESRD group was lower than that in the control group [17.39% vs. 21.20%; χ2=8.264, P=0.004, OR=0.783, 95%CI (0.662, 0.925)], and the frequency of HLA-DQB1*04 allele in the ESRD group was higher than that in the control group [7.41% vs. 5.46%; χ2=5.867, P=0.015, OR=1.386, 95%CI (1.063, 1.807)]. The frequencies of 10 haplotypes, including HLA-A*11-B*39, HLA-DRB1*15-DQB1*06, and HLA-DRB1*04-DQB1*04, were significantly different between the ESRD group and the control group (P<0.05), among which 9 haplotypes were possibly susceptible to ESRD and 1 haplotype was possibly protective. Conclusions HLA gene polymorphism is closely related to the susceptibility to ESRD. HLA-B*39 and HLA-DQB1*04 may be susceptible genes for ESRD in Sichuan Han patients, while HLA-DQB1*06 may be a protective gene. In addition, 10 HLA haplotypes are possibly associated with the susceptibility to ESRD in Sichuan Han patients.
ObjectiveTo explore the application value of plasma Epstein-Barr virus (EBV) DNA test in the clinical diagnosis of patients with nasopharyngeal carcinoma in non-high-incidence areas of Southwest China and its significance for monitoring patients after treatment. MethodsA total of 235 patients diagnosed with non-keratinized nasopharyngeal carcinoma between January 2014 and December 2015 were retrospectively collected. The plasma EBV-DNA test rate of the nasopharyngeal carcinoma patients before treatment, the positive rates of the plasma EBV-DNA test before treatment and within 6 months of treatment, and the relationship between the positivity of plasma EBV-DNA within 6 months of treatment and the prognosis of nasopharyngeal carcinoma were analyzed. ResultsThe plasma EBV-DNA test rate of the nasopharyngeal carcinoma patients before treatment was 69.79% (164/235), with a positive rate of 90.85% (149/164). A total of 131 patients were tested for EBV-DNA within 6 months of treatment, whose positive rate was 89.31% (117/131) before treatment and 21.37% (28/131) within 6 months of treatment, respectively, with a statistically significant difference (P<0.001). Comparing the prognosis of EBV-DNA positive patients and negative patients within 6 months of treatment, the difference in 3-year recurrence rate between the two groups was not statistically significant (10.71% vs. 3.88%, P=0.341); however, the 3-year metastasis rate (21.43% vs. 4.85%, P=0.016) and the 3-year disease progression rate (32.14% vs. 6.80%, P=0.001) of the EBV-DNA positive patients were higher than those of the EBV-DNA negative patients, and the log-rank test slao showed that the 3-year progression-free survival rate (67.86% vs. 93.20%, P<0.001) and the 3-year metastasis-free survival rate (78.57% vs. 95.15%, P=0.004) of the EBV-DNA positive patients were lower than those of the EBV-DNA negative patients. There was no statistically significant between-group difference in the 3-year progression-free survival curve when grouped by age, gender, or TNM staging (P>0.05).ConclusionsFor patients with non-keratinized nasopharyngeal carcinoma in non-high-incidence areas of Southwest China, EBV-DNA detection is important for the screening and diagnosis of nasopharyngeal carcinoma, and the positivity of EBV-DNA test within half a year of treatment is an important factor affecting the prognosis and progression of patients. Plasma EBV-DNA levels should be monitored regularly before and after treatment.