Relationship between genetic polymorphisms of IL-10 promoter and antituberculosis drug-induced liver injury / 中华疾病控制杂志

@# Objective To investigate the relationship between interleukin 10 (IL-10) -592 (rs1800872) and -819 (rs1800871) promoter genetic polymorphisms and the susceptibility of antituberculosis drug-induced liver injury (ADLI). Methods A case-control study was conducted. Epidemiology survey data and peripheral blood samples were obtained from the patients. Two IL-10 gene polymorphisms (-592 A/C and 819 C/T) were genotyped with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) in Chinese Han ADLI subjects (n=180) and sex matched by frequency matching in control subjects (n=180). Results No significant differences in genotypes of IL-10 -592 site and IL-10 -819 site between ADLI group and that of the control group were noticed (all P>0.05). The mutant alleles -592 C of IL-10 gene polymorphism was significantly higher in ADLI subjects compared to controls, and in dominant model, the frequency of CC+AC genotype was 1.62 higher among the cases than controls (all P<0.05). Significant difference in allele -819 C/T between the ADLI group and the control group were not found (P=0.190). The polymorphisms at -819 C/T and -592 A/C variants of IL-10 gene were found to be good linkage disequilibrium. The CC haplotype represent genetic risk factor (OR=1.37, 95% CI: 1.02-1.85) and CA haplotype represent genetic protect factor (OR=0.49, 95% CI: 0.34-0.70) for ADLI in the subjects. Conclusions The polymorphisms in IL-10 gene -592 A/C and -819 C/T are associated with ADLI.

Methylation of GSTP1 promoter region in hepatocellular injury induced by isoniazid / 国际药学研究杂志

Objective To investigate the relationship between methylation of CpG island in glutathione S-transferase P1(GSTP1) promoter region and injury induced by isoniazid in HL-7702 cells.Methods HL-7702 cells were divided into the control group and three isoniazid groups(200,400,800 mg/L).Colorimetric method was used to detect the activity level of lactate dehydrogenase in the medium of HL-7702 cells;the mRNA expression of GSTP1,DNA methyltransferases 1(DNMT1),DNMT3a and DNMT3b were de?tected by real-time fluorescence quantitative PCR;the protein expression levels of DNMT1,DNMT3a and DNMT3b were detected by enzyme-linked immunosorbent assay;the methylation of the CpG island in the GSTP1 promoter region was determined by the bisulfite sequencing PCR.Results The activity level of lactate dehydrogenase in supernatants of the HL-7702 cells in isoniazid group(400, 800 mg/L)was higher than that in the control group(P<0.01).Compared with the control group,the mRNA expression of DNMT 1、3a、3b and GSTP1 were elevated in 400 and 800 mg/L isoniazid groups(P<0.05,P<0.01).The proteins expression of DNMT1 and 3a in the 400 and 800 mg/L isoniazid groups were higher than that in the control group(P<0.05,P<0.01),and the protein expression of DNMT 3b in the 800 mg/L isoniazid groups were higher than that in the control group(P<0.01).The methylation level of CpG is?land in GSTP1 promoter region of three isoniazid groups were decreased.Conclusion The CpG island in the promoter of GSTP1 has hypomethylation in hepatocyte cells damaged by isoniazid.

High Physical Activity is Associated with an Improved Lipid Profile and Resting Heart Rate among Healthy Middle-aged Chinese People / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effects of physical activity (PA) on dyslipidemia and elevated resting heart rate (RHR) in a large-scale cross-sectional study in China.</p><p><b>METHODS</b>We recruited community-based individuals who were 40-60 years old using a cluster sampling method. The PA levels of the participants were classified as low, moderate, or high, using the International Physical Activity Questionnaire. Dyslipidemia was defined as the detection of abnormalities in lipid indicators, and 4 lipid parameters were evaluated using fasting blood samples. Multivariate logistic regression analyses were used to evaluate the associations of PA with dyslipidemia and RHR.</p><p><b>RESULTS</b>A total of 10,321 participants (38.88% men) were included in this study. The percentages of individuals with high, moderate, and low PA levels were 46.5%, 43.9%, and 9.6%, respectively. In both men and women, high PA provided odds ratios of 0.88 [95% confidence interval (CI): 0.83, 0.94] for dyslipidemia and 0.82 (95% CI: 0.73, 0.92) for elevated RHR, compared to participants with low PA.</p><p><b>CONCLUSION</b>Our data suggested that substantial health benefits (related to dyslipidemia and elevated RHR) occurred at higher intensity PA, with greater energy consumption, in middle-aged Chinese people, and particularly in men.</p>

Relationship between the polymorphisms of UGT1A6 genes and anti-tuberculosis drug induced hepatic-injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the polymorphisms of UGT1A6 genes and anti-tuberculosis drug induced hepatic-injury (ADIH).</p><p><b>METHODS</b>202 cases and 239 controls were collected and a case-control study was conducted. Information on related risk factors of tuberculosis was collected. The genotypes of UGT1A6-19T/G, UGT1A6-308C/A and UGT1A6-541A/G genetic polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism technique (PCR-RFLP) in patients received anti-tuberculosis therapy. The Hha I, Dpn II and Nsi I enzyme were employed. Univariate and multivariate conditional logistic analyses were conducted using SPSS13.0 for windows software.</p><p><b></b>RESULTS</p><p><b>RESULTS</b>The allele frequency of gene UGT1A6-19T/T, UGT1A6-19T/G, UGT1A6-19G/G, GT1A6-308C/C, UGT1A6-308C/A, UGT1A6-308A/A, UGT1A6-541AA, UGT1A6-541A/G and UGT1A6-541G/G in ADIH group were 51.5%, 39.6%, 8.9%, 52.0%, 40.6%, 7.4%, 57.9%, 33.7%, 8.4% and 71.1%, 25.5%, 3.3%, 79.1%, 19.2%, 1.7%, 79.5%, 19.2%, 1.3% in control group, respectively. Univariate analysis demonstrated that the frequency of UGT1A6-19T/G, UGT1A6-308C/A and UGT1A6-541A/G genotype in cases were significantly higher than that in controls (P less than 0.05).</p><p><b>CONCLUSION</b>A positive association is found between UGT1A6 genotype and the occurrence of ADIH. The synergetic effect is proved on susceptibility to pulmonary tuberculosis between UGT1A6 mutant genotypes.</p>

Association of TNF-alpha-238G/A and 308 G/A gene polymorphisms with pulmonary tuberculosis among patients with coal worker's pneumoconiosis / 生物医学与环境科学（英文）

<p><b>OBJECTIVES</b>Tumor necrosis factor-alpha (TNF-alpha) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-alpha gene polymorphism with pulmonary tuberculosis (TB) among patients with coal worker's pneumoconiosis (CWP).</p><p><b>METHODS</b>A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-alpha gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP). Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher's exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplicative model with combined OR. All data were analyzed using SAS version 8.2 software.</p><p><b>RESULTS</b>No significant difference in frequency of the TNF-alpha-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls (chi2 = 5.44, P = 0.07). But difference in frequency of the TNF-alpha-308 A allele was identified between them (chi2 = 5.14, P = 0.02). No significant difference in frequencies of the TNF-alpha-238 genotype and allele (P = 0.23 and P = 0.09, respectively) was found between cases and controls either, with combined (GG and AA) OR of 3.96 (95% confidence interval of 1.30-12.09) at the -308 locus of the TNF-alpha gene, as compared to combination of the TNF-alpha-238 GG and TNF-alpha-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-alpha-238 GG and TNF-alpha-308 GA genotypes was 1.98 (95% CI of 1.06-3.71) for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-alpha-308 GG genotype and body mass index (OR = 4.92), as well as an interaction between the TNF-alpha-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-alpha-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated.</p><p><b>CONCLUSIONS</b>TNF-alpha-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-alpha-238 A allele was otherwise.</p>

A study of chronic hepatitis B infection superinfected with hepatitis E infection / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To compare the influence of hepatitis E virus (HEV) infection on the replication of hepatitis B virus (HBV) by observing clinical features, the relationship between the number of HBV DNA copies in serum, the degree of hepatic function impairments and prognosis of chronic hepatitis B patients with hepatitis E superinfection.</p><p><b>METHODS</b>One hundred and fifteen chronic hepatitis B (CHB) patients and 115 CHB patients with hepatitis E (HE) superinfection were studied and compared. 74 liver tissue biopsy samples of the CHB and 51 of the CHB-HE sufferers were obtained. HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HBc-IgG, anti-HBc-IgM, HBV DNA and anti-HEVIgM were detected respectively by enzyme linked immunosorbent assay and polymerase chain reaction.</p><p><b>RESULTS</b>The number of HBV DNA copies in sera in the CHB-HE group and the severity of the clinical features were significantly higher than those in the CHB group. The former group had a poorer prognosis with a 49.6% occurrence rate of severe hepatitis and a 25.2% death rate while in the latter group the corresponding rates were just 4.4% and 1.7%.</p><p><b>CONCLUSION</b>Re-infection with HEV, in those CHB patients, severely damaged their hepatic functions and increased their mortality; the older the patient and the higher the level of HBV DNA, the poorer the prognosis.</p>

Study on the association of INT4 and 3'UTR polymorphism of natural-resistance-associated macrophage protein 1 gene with susceptibility to pulmonary tuberculosis / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association between natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms and susceptibility to pulmonary tuberculosis (TB) in Han nationality from Northern part of China.</p><p><b>METHODS</b>A 1:1 matched case-control study was adopted. Polymerase chain reaction and restriction fragment length polymorphism technique were used to type the two NRAMP1 polymorphisms: INT4 and 3'UTR. Information on environmental-related risk factors and pathological changes of tuberculosis was collected using a pre-tested standard questionnaire. Univariate and multivariate conditional logistic analyses were conducted using SPSS for window software.</p><p><b>RESULTS</b>A sample consisting 124 pairs of cases and controls was studied. Univariate analysis demonstrated that the 3'UTR TGTG+/del genotype occurred more frequently in the cases than in the controls, with crude OR (95% CI) being 2.923 (1.557 - 5.487). No significant association was observed between TB and INT4 polymorphism. In multivariate analysis, associations of TB and 3'UTR TGTG+/del genotype remained, after adjusting for scar of bacillus Calmette-Guérin vaccine, marriage status, body mass index and exposure history. Adjusted OR (95% CI) was 2.955 (1.369 - 6.381). Again, no significant association between INT4 polymorphism and TB was found. Among different INT4 genotypes, the pathological characters of pulmonary tuberculosis were also found different (chi(2) = 9.634, P < 0.05).</p><p><b>CONCLUSION</b>Polymorphism of 3'UTR locus in NRAMP1 gene might affect their susceptibility to TB in Han nationality living in the northern part of China, and polymorphism of INT4 might affect the pathological characters of tuberculosis.</p>

Study on mannose-binding protein gene polymorphisms and susceptibility to pulmonary tuberculosis / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the association between the genetic polymorphisms of mannose-binding protein (MBP) alleles and susceptibility to pulmonary tuberculosis.</p><p><b>METHODS</b>125 pulmonary tuberculosis cases and 198 healthy controls were collected. A case-control study was conducted. Three structural gene mutations in exon 1 of MBP gene (codon 52, codon 54 and codon 57) were studied. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was carried out in the polymorphism in MBP alleles. Information on related risk factors of tuberculosis was collected, using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted with SPSS software package.</p><p><b>RESULTS</b>The frequencies of mutant heterozygote or homozygote of MBP-52, 54, 57 were 8.0%, 7.2% and 0.4% for cases and 5.3%, 4.3%, 0.5% for controls, respectively. The distribution of mutant genotypes of MBP did not show significant difference between tuberculosis patients and control by Mantel-Haenszel chi2 on sex. The univariate analysis demonstrated that body mass index, marital status, vaccinal vestige, bacillus of Calmette-Guerin vaccine immunization, contacted with pulmonary tuberculosis patients, familial traits were the risk factors of pulmonary tuberculosis. After adjusting those related environmental factors in the multivariate logistic analyses, the total MBP (MBP-52, MBP-54 and MBP-57) and MBP-52 heterozygote genotypes were significantly overrepresented in cases, with adjusted OR (95% CI) being 2.182 (1.058-4.499) and 2.574 (1.028-6.446).</p><p><b>CONCLUSION</b>Total MBP and MBP-52 mutant genotypes might be associated with the susceptibility to pulmonary tuberculosis.</p>

Cloning and characterization of a full-length HIV-1 genome of a prevalent subtype B-Thai strain in Henan Province / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To clone, identify and phylogenetically characterize a clade B-Thai HIV isolate representing the most prevalent virus in Henan province.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMCs) from an HIV-1 infected patient in Henan Province were separated, and co-cultivated with phytohemagglutinin-stimulated healthy donor PBMCs. Proviral DNA was extracted from productively infected PBMCs. The full-length HIV-1 genome was amplified by using the LA Tag long template PCR system. Primers were positioned in conserved regions within the HIV-1 long terminal repeats. Purified PCR products were T-A ligated into a pWSK29-T vector(CNHN 24 clone). Three recombinant clones containing virtually full-length HIV-1 genome were identified by PCR. The full-length genome was sequenced by using the primer-walking approach. Nucleotide sequence similarities were calculated by the local-homology algorithm. Phylogenetic trees of gag, pol and env reading frames were constructed using the Phylip software.</p><p><b>RESULTS</b>HIV-1 C3V4 sequences indicate that the epidemic in this area was B-Thai subtype. V3 loop multiple amino acid sequence alignments showed amino acid alterations at nine positions. The 9,010 bp genomic sequence derived from isolate CNHN 24 contained all known structural and regulatory genes of an HIV-1 genome. No major deletions, insertions, or rearrangements were found. The highest homologies of the gag, pol, vpr, and vif reading frames to the corresponding clade B-Thai RL 42 sequences were 95.42%-97.08%. Phylogenetic trees showed the closest relationship of CNHN 24 and RL 42.</p><p><b>CONCLUSION</b>The cloning and characterization of a virtually full-length HIV-1 B-Thai subtype in central China was completed in our laboratory. The data should be helpful to future studies on the genetic diversity of HIV-1.</p>

Study on factors associated with heterosexual-transmission of human immunodeficiency virus in central China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the factors of the human immunodeficiency virus (HIV) associated with sexual-transmission in central China.</p><p><b>METHODS</b>(1) Cross-sectional study: couples that one was HIV positive were selected in Henan and Hebei province of China. The couples must be 20 - 50 years old with normal function on sexual intercourse. Cordant couples that subsequently infected partners were at risk of infection solely through sexual contact with the HIV-seropositive partner and the discordant couples that the seronegative partners were at risk of infection solely through sexual contact with the HIV-seropositive partner, were selected. Plasma viral load, CD4 cell count were tested. (2) Case-control study was used to compare 7 sexual transmitted cases and 56 nontransmitted controls with respect to the frequency of sexual intercourse, plasma viral load and CD4 cell count.</p><p><b>RESULTS</b>(1) A total of 87 couples that at least one partner was HIV positive were recruited include 56 discordant couples and 7 cordant couples with whom sexual transmission had happened. The rate of sexual transmission was 11.1% among those at the risk of sexual transmission. (2) Of the discordant couples, male positive rate 25%, female positive was 75%. (3) The risk for transmission was higher in those couples with the frequency of unprotected vaginal sexual intercourse (> or = 4 times per month) than the reference group (< 4 times per month) (Fisher's exact test, P = 0.047, OR = 8.0). Median plasma viral load was significantly higher in the antecedent infected partners of cordant couples than the positive partner of discordant couples (378,285.71 vs 136,578.57 copies/ml, t = 3.591, P < 0.01). The odds ratio was 22.0 for plasma viral load > or = 100,000 copies/ml compared with the reference group of < 100 000 copies/ml (Fisher's exact test, P = 0.016). The CD4 cell count and CD4/CD8 of the transmitted group were significantly lower than that of the nontransmitted (t = 2.767, P < 0.05; t = 6.06, P < 0.05).</p><p><b>CONCLUSIONS</b>The frequencies of heterosexual-transmission in central China were relatively low. The risk of heterosexual transmission was related to the frequency of sexual intercourse. Higher plasma viral load and lower CD4 count was strongly correlated with high risk of heterosexual transmission.</p>