Chuanmin Tao

Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population

MicroRNAs (miRNA) are thought to play important roles in the pathogenesis of diseases. Single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics via altering their target selection and/or expression, resulting in functional and/or phenotypic changes. We decided to investigate the genetic association with pulmonary tuberculosis with 2 nucleotide variations within corresponding microRNAs regulating the Toll-like receptor (TLR)-mediating signal pathway. MiRNAs potentially regulating the TLR-mediating signal pathway were predicted via bioinformatics. Finally, 2 SNPs, rs2910164 G>C and rs3746444 T>C within miR-146a and miR-499, were selected as candidates in accordance with some criteria. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and validated by sequencing to demonstrate their association with susceptibility to pulmonary tuberculosis (PTB) in 337 PTB cases and 738 healthy controls, including 318 Tibetan and 757 Han individuals. Bioinformatics databases were searched to support the association between miRNAs and PTB. There was no association between rs3746444 and PTB risk (p = 0.118) in the Han population, but subjects carrying the C allele exhibited decreased PTB risk (odds ratio [OR] = 0.403 [95% confidence interval (95% CI) 0.278-0.583]). However, there was an association between rs3746444 and PTB in the Tibetan population, and individuals carrying the C allele exhibited increased PTB risk (OR = 1.870 [95% CI 1.218-2.871]). A polymorphism (rs2910164 G>C) indicated an association with PTB risk in both Tibetan (p = 0.031) and Han (p = 0.000) populations. However, the role of the G allele of rs2910164, like the C allele in rs3746444, differed in the Tibetan (OR = 1.509, p < 0.05) and Han (OR = 0.575, p < 0.05) groups. This is the first report to suggest that a genetic association with pulmonary tuberculosis with SNPs within the corresponding miRNAs potentially regulates the TLR signal pathway. It is interesting that both the G allele (rs2910164) and the C allele (rs3746444) play different roles in 2 populations. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype.

Efficacy and Safety of Polymyxins for the Treatment of Acinectobacter baumannii Infection: A Systematic Review and Meta-Analysis

Background Multi-drug resistance among Acinetobacter baumannii increases the need for polymyxins. We conducted a meta-analysis aimed to assess the efficacy and safety of polymyxins for the treatment of Acinetobacter baumannii infection. Methods We searched PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, Chinese Biomedical Literature Database up to November 1, 2013, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies. Randomized controlled trials and cohort studies were considered for inclusion. Data were extracted on clinical response, microbiological response, mortality, length of stay and adverse events. Results 12 controlled studies, comparing 677 patients, were included. Although clinical (odds ratio 1.421, 95% confidence interval 0.722–2.797) and microbiological (OR 1.416, 95% CI 0.369–5.425) response rates favored the polymyxins group, these differences were not significant. Treatment with polymyxins vs. controls did not affect hospital mortality (OR 0.506, 95% CI 0.101–2.536), lengths of hospital stay (standard mean difference −0.221, 95% CI 0.899–0.458) or nephrotoxicity (OR 1.192, 95% CI 0.436–3.261). The combination of polymyxins with other antibiotics achieved similar clinical response rates to its monotherapy regimen (OR 0.601, 95% CI 0.320–1.130). Conclusions Our results suggest that polymyxins may be as safe and as efficacious as standard antibiotics for the treatment of A. baumannii infection. There is no strong evidence that combination regimen of polymyxins is superior to monotherapy regimen.

Association of HLA-DP/DQ and STAT4 Polymorphisms with HBV Infection Outcomes and a Mini Meta-Analysis

Background Though HLA-DP/DQ is regarded to associate with HBV susceptibility and HBV natural clearance, its role in hepatocellular carcinoma (HCC) development is obscure. And the role of STAT4 in HBV susceptibility and clearance as well as HCC development is still contentious. Therefore, we conducted this study, aiming to clarify these obscure relationships. Methods We recruited 1312 Chinese Han subjects including healthy controls, HBV carriers and HCC patients in the experiment stage. The meta-analysis included 3467 HCC patients and 5821 HBV carriers to appraise the association with HCC development. Results Consistent with previous studies, HLA-DP/DQ associated with HBV susceptibility and HBV natural clearance (p<0.05). However, the experiment showed that HLA-DP rs3077, rs9277535 and rs7453920 did not associate with HCC development (dominant model, rs3077, ORu200a=u200a0.86, 95%CIu200a=u200a0.62–1.18; rs9277535, ORu200a=u200a0.94, 95%CIu200a=u200a0.68–1.30; rs7453920, ORu200a=u200a0.75, 95%CIu200a=u200a0.44–1.27). Meta-analysis again consolidated this conclusion (allele model, rs3077, ORu200a=u200a0.94, 95%CIu200a=u200a0.87–1.02; rs9277535, ORu200a=u200a1.04, 95%CIu200a=u200a0.97–1.11; rs7453920, ORu200a=u200a0.89, 95%CIu200a=u200a0.76–1.02). As for STAT4 rs7574865, we did not find any significant association with HBV susceptibility (ORu200a=u200a0.91, 95%CIu200a=u200a0.66–1.26) or HBV natural clearance (ORu200a=u200a1.13, 95%CIu200a=u200a0.86–1.49). Moreover, current data failed to acquire positive connection of rs7574865 with HCC development (experiment, ORu200a=u200a0.86, 95%CIu200a=u200a0.62–1.19; meta-analysis, ORu200a=u200a0.87, 95%CIu200a=u200a0.74–1.03), which may be due to the small sample size. Conclusions HLA-DP/DQ polymorphisms (rs3077, rs9277535, rs7453920) did not associate with HCC development, but did correlate with HBV susceptibility and HBV natural clearance. STAT4 rs7574865 seemed not to correlate with HBV susceptibility or natural clearance. And it seemed rather ambiguous in its role on HCC development at present.

Association between two single nucleotide polymorphisms at corresponding microRNA and schizophrenia in a Chinese population

Numerous linkage and association studies have been performed to identify genetic predispositions to schizophrenic (SCZ) in different populations, but its genetic basis remains unclear. Some findings may provide a clue in understanding the association between abnormal immunity and SCZ. MicroRNA (miRNA) involves in regulating both schizophrenic and immunity as previous reported. And single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics, resulting in functional and/or phenotypic changes. So two SNPs (hsa-pre-mir-146a rs2910164 G>C and hsa-mir-499 rs3746444 T>C) at two miRNAs, were genotyped to demonstrate their association with susceptibility to SCZ. Polymorphisms were analyzed among 268 Chinese schizophrenic patients and 232 healthy controls by PCR-RFLP and validated by sequencing. No association was found between the two polymorphisms and SCZ either in cases or in controls. SCZ patients with family history showed significant increase of the G allele frequency of rs2910164 in comparison to those without (Pxa0=xa00.018). The CC genotype frequency of rs3746444 was also higher in the patients having hallucinations than those without hallucinations (Pxa0=xa00.012). In addition, patients carrying CC genotype of rs3746444 were more likely to be lack of motivation in comparison to normal controls (Pxa0=xa00.042). Allele and genotype frequency of rs2910164 showed no significant difference between patients and normal subjects or between patients with and without clinical variables. Although patients carrying CC genotype of rs3746444 were found to be more likely to develop hallucination and individuals carrying C allele to lack motivation, there is lacking association between SCZ and the two SNPs at miRNAs, which may regulate immune response.

Association of the gene polymorphisms in sodium taurocholate cotransporting polypeptide with the outcomes of hepatitis B infection in Chinese Han population

OBJECTIVEnIn recent years, sodium taurocholate cotransporting polypeptide (NTCP) was newly identified as a hepatitis B virus (HBV) receptor, which partly shed light on the reason for HBV hepatotropism and its host specificity. However, the related researches were limited to in vitro or animal experiments. Therefore, this study aimed to investigate the association of NTCP polymorphisms with HBV natural course in humans.nnnMETHODSnAccording to their serological and clinical characteristics, 933 Chinese Han individuals were divided into two major groups, 352 viral clearance controls and 581 persistently infected patients. The latter one included 186 hepatocellular carcinoma (HCC) and 395 non-HCC subjects. A total of five single nucleotide polymorphisms (SNPs) were selected from HapMap dataset and genotyped by high resolution melting (HRM) curve method.nnnRESULTSnThe rs7154439 AA genotype was observed slightly more common in viral clearance group than in persistently infected group [16 (4.5%) subjects vs. 10 (1.7%) subjects. p=0.008, adjusted odds ratio (AOR)=0.33, 95% confidence interval (CI)=0.15-0.75 in a codominant model; and p=0.006, AOR=0.32, 95% CI=0.14-0.72 in a recessive model]. While the rs4646287 AA genotype was observed slightly more frequent in HCC group than in non-HCC group [6 (3.2%) subjects vs. 1 (0.3%) subject. p=0.018, AOR=15.74, 95% CI=1.59-155.54 in a codominant model; and p=0.018, AOR=15.91, 95% CI=1.61-157.01 in a recessive model]. There were no statistically significant differences of allele or haplotype distribution between any two groups.nnnCONCLUSIONSnThis study suggests that polymorphisms in the NTCP region may be associated with the natural course of HBV infection. The rs7154439 AA genotype was associated with HBV clearance, while the rs4646287 AA genotype was associated with HCC occurrence. However, considering the sample size is relatively small, larger studies, especially through multicenter collaboration will be needed to fully validate the significance of these findings.

TIRAP C539T polymorphism contributes to tuberculosis susceptibility: evidence from a meta-analysis.

BACKGROUNDnToll-interleukin 1 receptor domain containing adaptor protein (TIRAP), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, is highly involved in the activation and coordination of the anti-mycobacterial immune response. We performed a meta-analysis to assess the association between TIRAP C539T polymorphism and tuberculosis (TB) risk.nnnMETHODSnA systematic literature search for relevant studies up to February 27, 2014 was conducted in PUBMED, EMBASE, Web of science, CNKI, VIP, and Wanfang database. The association between gene and disease was assessed using odds ratios (ORs) with 95% confidence intervals (95%CIs) based on five genetic models.nnnRESULTSnA total of 16 qualified studies were enrolled in this meta-analysis. The results of pooling all studies detected statistically resistance of TIRAP C539T mutants to TB risk (T vs. C: OR 0.80, 95%CI 0.65-0.97; TC vs. CC: OR 0.71, 95%CI 0.55-0.92; TT+TC vs. CC: OR 0.74, 95% CI 0.58-0.94). Further subgroup analyses by ethnicity also demonstrated reduced risk of TB in European population (T vs. C: OR 0.71, 95%CI 0.52-0.95; TC vs. CC: OR 0.56, 95%CI 0.35-0.91; TT+TC vs. CC: OR 0.61, 95%CI 0.40-0.92), whereas no such effects were observed in other ethnicities.nnnCONCLUSIONnThis present meta-analysis suggests TIRAP C539T polymorphism is significantly correlated with reduced risk of TB infection, with stronger effect in European. Additional well-designed, larger-scale epidemiological studies among different ethnicities are needed.

Prevalence of Hepatitis B Virus Genotypes and their Relationship to Clinical Laboratory Outcomes in Tibetan and Han Chinese

This study was designed to investigate the prevalence of hepatitis B virus (HBV) genotypes in Tibetan and Han nationalities in Sichuan Province, China, and their clinical significance. Sera from 376 patients (286 Han nationals, 90 Tibetan nationals) were genotyped by polymerase chain reaction. Of the 286 Han nationals, 127 were HBV asymptomatic carriers, 90 were symptomatic patients and 69 had hepatocellular carcinoma. The distribution of HBV genotypes was related to geography as well as ethnicity. The HBV genotype frequencies were: B, 57.9%; C, 16.0%; and BC, 26.1%. Association studies between genotypes and clinical laboratory outcomes showed HBV genotype C to be more virulent. There was a higher prevalence of mixed genotype BC in Tibetan nationals compared with Han nationals. There was no synergistic effect in terms of virulence in patients co-infecte with genotypes B and C.

Performance evaluation of a new fourth-generation HIV Ag/Ab combination electrochemiluminescence immunoassay – evaluation of a new HIV assay

A new fourth-generation HIV Ag/Ab electrochemiluminescence immunoassay for screening of HIV infection, the Elecsys® HIV Combi PT (Roche Diagnostics, Penzberg, Germany) assay, is going to be commercially available in clinical laboratories in China. This assay was evaluated and compared with two commonly used assays: Elecsys® HIV Combi assay and the Livzon anti-HIV-1/2 ELISA. Commercially available panels and 30 established HIV infection samples were tested to evaluate the sensitivity. In addition, a total of 675 routine clinical samples were collected and tested in West China Hospital to compare the specificity. Any reactive result from a screening test was retested and all reactive retested samples were confirmed with Western blot assay, Elecsys® HIV Ag test, Elecsys® HIV Ag confirmatory test or HIV-1 RNA NAT testing. According to the results of the HIV seroconversion panels, the Elecsys® HIV Combi PT could detect seroconversion at the same bleed or at least one bleed earlier compared to the other two assays. Among the 675 clinical samples, most results were consistent except for one specimen with a false-negative result using Elecsys® HIV Combi assay. In conclusion, the Elecsys® HIV Combi PT has shown satisfactory sensitivity and specificity to be a screening test for HIV infection.

Comparative Performance of Electrochemiluminescence Immunoassay and EIA for HIV Screening in a Multiethnic Region of China

Background The recent approval of 4th generation HIV tests has forced many laboratories to decide whether to shift from 3rd to these tests. There are limited published studies on the comparative evaluation of these two different assays. We compare the performance of fourth-generation electrochemiluminescence immunoassay (ChIA) and third-generation enzyme linked immunosorbent assay (EIA) for human immunodeficiency virus (HIV) screening and gauge whether the shift from EIA to ChIA could be better in a multiethnic region of China. Methodology/Principal Findings We identified a large number of routine specimens (345,492) using two different assays from Jan 2008 to Aug 2011 in a teaching hospital with high sample throughput. Of the 344,596 specimens with interpretable HIV test results, 526(0.23%) of 228,761 using EIA and 303(0.26%) of 115,835 using ChIA were HIV-1 positive. The false-positive rate of EIA was lower than that of ChIA [0.03% vs. 0.08%, odds ratio 0.33 (95% confidence interval 0.24, 0.45)]. The positive predictive value (PPV) of EIA (89.6%) was significantly higher than that of ChIA (76.1%) (<0.001), reflecting the difference between the two assays. The clinical sensitivities of two assays in this study were 99.64% for EIA and 99.88% for ChIA. Conclusion Caution is needed before shifting from 3rd to 4th generation HIV tests. Since none of these tests are perfect, different geographic and ethnic area probably require different considerations with regard to HIV testing methods, taking into account the local conditions.

The association of interleukin-10 -1082, -819, -592 polymorphisms and tuberculosis risk

Objectives: To assess the association between interleukin (IL)-10 -1082, -819, -592 polymorphisms and tuberculosis (TB) risk. Methods: This study was conducted between July and October 2014 in West China Hospital, Chengdu, Sichuan, China. We searched and collected data from PUBMED, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP, and WANGFANG up to October 2014. Results: A total of 37 studies were enrolled, including 8625 TB cases, and 9928 healthy controls. The IL-10-1082G/A polymorphism was found to be associated with TB susceptibility in Caucasian (GG versus GA+AA, odds ratio [OR] - 1.83, 95% confidence interval [CI] - 1.03-3.24). The IL-10-819C/T polymorphism was related to TB susceptibility among Asians (C versus T, OR - 0.88, 95% CI - 0.81-0.97; CC versus TT: OR - 0.79, 95% CI - 0.64-0.97; CC+CT versus TT: OR - 0.87, 95% CI - 0.77-0.98; CC versus CT+TT: OR - 0.82, 95% CI - 0.68-0.98). The IL-10-592C/A polymorphism was in association with TB susceptibility in Asians (C versus A: OR - 0.74, 95% CI - 0.65-0.85; CC versus AA: OR - 0.55, 95% CI - 0.41-0.75; CA versus AA: OR - 0.73, 95% CI - 0.60-0.89; CC+CA versus AA: OR - 0.69, 95% CI 0.58-0.83; CA versus AA: OR - 0.66, 95% CI 0.51-0.86), Caucasian (C versus A: OR - 1.25, 95% CI - 1.08-1.45; CC versus CA+AA: OR-1.48, 95% CI - 1.16-1.89), and Europeans (C versus A: OR - 1.31, 95% CI - 1.02-1.67; CC versus AA: OR - 1.88, 95% CI - 1.05-3.37). Conclusion: This meta-analysis suggests that IL-10-1082G/A, IL-819C/T, and IL-592C/A polymorphisms might be associated with TB susceptibility in certain ethnicities.