Xin Hu

Association Between Two Genetic Variants in miRNA and Primary Liver Cancer Risk in the Chinese Population

MicroRNAs (miRNAs) play an important role in the growth and development of human beings. Single nucleotide polymorphisms (SNPs) within miRNA could change their production or affinity with target genes, thus leading to malignant diseases. This case-control study conducted in Western China aimed to explore the relationship between polymorphisms in miR-146a (rs2910164 G>C) and miR-499 (rs3746444 T>C) and primary liver cancers in the Chinese population. 186 primary liver cancer cases and 483 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism. No significant differences were observed between distributions of the two SNPs and susceptibility of primary liver cancer or diverse clinicopathologic features. However, we found that patients with genotype CG of the SNP in miR-146a tended to have earlier onset and better liver function than patients with genotype CC (average age: 49.9 vs. 54.9, p=0.038; average Child-Pugh grade: 5.55 vs. 6.15, p=0.021), and further analysis showed that patients who had at least one G allele were diagnosed at an earlier age (average age: 49.6 vs. 54.9, p=0.022) and had better liver function (average Child-Pugh grade:5.60 vs. 6.15, p=0.026). Our data suggested lack of association between the two SNPs and primary liver cancer risk, though, interestingly, the miR-146a SNP may influence the age of onset and Child-Pugh grade.

Precore Mutation of Hepatitis B Virus May Contribute to Hepatocellular Carcinoma Risk: Evidence from an Updated Meta-Analysis

Background Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations. Methods We searched the commonly used databases both in English and Chinese till February 1st, 2012. Meta-analysis was performed in fixed/random-effects models using STATA 10.0. Publication bias was examined through Eggers test and Beggs funnel plot. Results In total, 85 case-control studies were included involving 16745 HBV-infected patients, of whom 5781 had HCC. Statistically significant correlations were observed in Precore mutation G1896A (ORu200a=u200a1.46, 95% confidence interval [CI]u200a=u200a1.15–1.85, PORu200a=u200a0.002), G1899A (ORu200a=u200a3.13, 95%CIu200a=u200a2.38–4.13, POR<0.001) and Pre-S mutation especially Pre-S1 deletion (ORu200a=u200a2.94, 95%CIu200a=u200a2.22 to 3.89) and Pre-S2 deletion (ORu200a=u200a3.02, 95%CIu200a=u200a2.03 to 4.50). Similar correlation existed between BCP double mutation A1762T/G1764A, T1753V, C1653T and HCC. In subgroup analysis, the Asians, genotype C or HBeAg positive patients with certain above mutations may be more susceptible to HCC. Besides, the mutations like G1896A and BCP double mutation may be associated with the progression of the liver diseases. Conclusions Precore mutation G1896A, G1899A, deletions in Pre-S region as well as the other commonly seen mutations correlated with the increased risk of HCC, especially in Asians and may predict the progression of the liver disease.

Meta-analysis of the effect of MDR1 C3435 polymorphism on tacrolimus pharmacokinetics in renal transplant recipients.

BACKGROUNDnThe published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of tacrolimus in different post transplant times; thus, the aim was to perform a meta-analysis of different post transplant times to investigate the influence of SNP C3435T on the tacrolimus pharmacokinetics.nnnMETHODSnA literature search was conducted to locate the relevant papers by using the PUBMED and EMBASE electronic source until 2011. The pharmacokinetic parameters, including dose administration, concentration and concentration to dose ratio were extracted and a meta-analysis was performed by using STATA10.0.nnnRESULTSnA total of 13 papers concerning 1327 individuals were included in the meta-analysis. The overall results showed SNP C3435T could influence the pharmacokinetic parameters in different post transplant times, the subjects with CC genotype had lower concentration dose ratio and need higher tacrolimus dose than the CT and TT genotype.nnnCONCLUSIONSnOur meta-analysis of available studies has demonstrated a definite correlation between the SNP C3435T in MDR1 gene and pharmacokinetics of tacrolimus. However, additional studies with large sample size and better study designs are warranted to verify our finding.

Donor or recipient TNF-A -308G/A polymorphism and acute rejection of renal allograft: A meta-analysis.

BACKGROUNDnResults from published studies on the association of donor or recipient TNF-A -308G/A polymorphism with acute rejection (AR) of renal allograft are inconsistent. We performed a meta-analysis to summarize the possible association.nnnMETHODSnStudies were identified by searching PUBMED, EMBASE and Chinese National Knowledge Infrastructure (CNKI) databases until March 22, 2011. Meta-analysis was performed in a fixed/random-effect model using Revman 5.0.25 and STATA10.0.nnnRESULTSnEight studies evaluating the association between donor TNF-A -308G/A polymorphism and acute rejection of renal allograft were identified. Pooled OR based on 460 cases (whose recipient developed AR) and 623 controls (whose recipient did not develop AR) was 1.44 (95% CI=1.05-1.99, p=0.03). No association was detected in the subgroup analysis based on ethnicity. 28 studies evaluating the association between recipient TNF-A -308G/A polymorphism and acute rejection were identified. Pooled OR based on 1411 cases (patients did not develop AR) and 2088 controls was 1.39 (95% CI=1.06-1.82, p=0.02). Two studies evaluating the association between recipient TNF-A -308G/A polymorphism and recurrent acute rejection were identified. Pooled OR based on 225 cases (patients with ≤1 AR) and 34 controls (patients with ≥2 AR) was 0.28 (95% CI=0.13-0.62, p=0.002).nnnCONCLUSIONSnOur meta-analysis provided evidence that TNF2 allele positive genotype of donor or recipient was associated with increased risk of incidence of acute rejection of renal allograft. Recipient TNF2 allele positive genotype is also associated with increased risk of recurrence of acute rejection of renal allograft. However, additional studies with large sample size and better study designs are warranted to verify our finding.

Association between IL-6 –174G/C polymorphism and acute rejection of renal allograft: Evidence from a meta-analysis

BACKGROUNDnResults from published studies on the association of donor or recipient IL-6 -174G/C (rs1800795) polymorphism with acute rejection (AR) of renal allograft are conflicting. We performed a meta-analysis to estimate the possible association.nnnMETHODSnStudies were identified by searching PUBMED and EMBASE until July 1, 2011. Meta-analysis was performed in a fixed/random effects model using Revman 5.0.25 and STATA10.0.nnnRESULTSnSeven studies addressing the association between donor high producer genotype (G/G and G/C) of IL-6 -174G/C polymorphism and acute rejection of renal allograft were identified. Pooled OR based on 341 cases (whose recipient developed acute rejection) and 702 controls (whose recipient did not develop acute rejection) was 0.59 (95% CI, 0.26-1.33; p=0.20), with a strong between-study heterogeneity. No association was observed in the subgroup analysis based on ethnicity. 13 studies evaluating the association between recipient IL-6 -174G/C polymorphism and acute rejection were identified. Pooled OR based on 451 cases (patients did not develop acute rejection) and 848 controls was 1.00 (95% CI=0.72-1.37; p=0.98), with a weak between-study heterogeneity.nnnCONCLUSIONSnDonor high producer genotype (G/G and G/C) of IL-6 -174G/C polymorphism had a tendency of decreased risk for acute rejection, although it was not statistically significant. Recipient high producer genotype was not associated with acute rejection of renal allograft. Additional well designed studies with larger sample size are needed to support our findings, especially for the association between donor high producer genotype (G/G and G/C) of IL-6 -174G/C polymorphism and acute renal allograft rejection.

Association between SNPs in microRNA-machinery genes and tuberculosis susceptibility in Chinese Tibetan population

Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis and remains a leading cause of morbidity and mortality caused by infectious agents worldwide. Although our current understanding of the pathogenesis of TB is far from clear, there is a growing body of evidence suggesting a genetic contribution to the etiology of TB. By analyzing 294xa0TB cases and 287 healthy controls in a Chinese Tibetan population, we used a candidate gene approach to evaluate the association between six single nucleotide polymorphisms (rs10719, rs3757, rs3742330, rs636832, rs7813, and rs3744741) in microRNA machinery genes and TB susceptibility. The genotypic distributions of rs3757 and rs3744741 in controls were not in accordance with the Hardy–Weinberg Equilibrium (Pxa0<xa00.05). Logistic regression analysis demonstrated that subjects carrying rs3742330 GG genotype had significantly decreased risk for TB than individuals carrying AA genotype [odds ratio (OR)xa0=xa00.31, 95xa0% confidence interval (CI) 0.12–0.75, Pxa0=xa00.004. Carrying the G allele of rs3742330 was associated with a 27xa0% decreased risk for TB (95xa0% CI 0.55–0.97, Pxa0=xa00.03). However, no significant associations were found for rs10719, rs636832 and rs7813. Computational modeling suggests that the rs3742330 lies within a predicted binding site (seed region) for microRNA-632 (miR-632) and that the G allele alters the affinity of microRNA-mRNA binding by disrupting the local structure of dicer 1, ribonuclease type III (DICER) mRNA, presumably allowing for upregulated DICER expression. Taken together, our data suggest that common genetic variations DICER may influence TB risk, possibly through miR-632-mediated regulation. Replication of our studies in other populations will strengthen our understanding of this association.

Clinical features, Outcomes and Molecular Profiles of Drug Resistance in Tuberculous Meningitis in non-HIV Patients

Tuberculous meningitis continues to be a serious problem for physicians because it is difficult to make an early diagnosis and the consequences of delaying treatment are severe. The objective of this study is to provide data for the optimization of diagnostic and timely treatment of tuberculous meningitis. Of the 401 human immunodeficiency virus (HIV)-negative tuberculous meningitis patients in our study, 332 were found to have an impaired blood brain barrier (82.8%). Nearly 17.0% of patients failed to be timely diagnosed. Headache (53.6%) and fever (48.6%) were the most common features, and Computed Tomography/Magnetic Resonance Imaging (CT/MRI) detected 96 patients (23.9%) with abnormal meningeal imaging. Cerebrospinal fluid real-time polymerase chain reaction was positive in 73.8% of the tuberculous meningitis patients, whereas, smears and cultures detected only 6.7% and 5.2%, respectively. Further analysis identified striking differences between drug-resistant and drug-susceptible tuberculous meningitis. Patients with drug resistance correlated with grave prognosis. Tuberculous meningitis diagnosis should overall embody clinical symptoms, laboratory and cerebral imaging findings, and more sensitive diagnostic approaches are still warranted. Our data suggest cerebrospinal fluid polymerase chain reaction for mycobacterial DNA and molecular drug susceptibility testing as routine assays for suspected tuberculous meningitis patients, and observation of the blood brain barrier function could be performed for individual management.

Status of drug-resistant tuberculosis in China: A systematic review and meta-analysis.

BACKGROUNDnWe conducted a systematic review and meta-analysis on drug-resistant tuberculosis in China to provide useful data for tuberculosis (TB) surveillance and treatment.nnnMETHODSnSeveral databases, including PubMed, Embase, and the Chinese Biological Medical Database, were systematically searched between January 1, 1999, and August 31, 2015, using strict inclusion and exclusion criteria.nnnRESULTSnThe corresponding drug-resistant TB prevalence between the new and previously treated cases was significantly different in almost all of the economic regions. The Eastern coastal region is the most developed economic region with the lowest total drug-resistant TB prevalence (any drug resistance: 28%; 95% confidence interval [CI], 25%-32%; multidrug resistance: 9%; 95% CI, 8%-12%) and the lowest number of new cases (any drug resistance: 21%; 95% CI, 19%-23%; multidrug resistance: 4%; 95% CI, 3%-5%). The Northwest is the least developed area with the lowest drug-resistant TB prevalence for previously treated cases (any drug resistance: 45%; 95% CI, 36%-55%; multidrug resistance: 17%; 95% CI, 11%-26%). The prevalence (multidrug and first-line drug resistance) exhibited a downward trend from 1996-2014. The extensively drug-resistant prevalence in China was 3% (95% CI, 2%-5%) in this review.nnnCONCLUSIONSnOverall, the status of drug-resistant tuberculosis in China is notably grim and exhibits regional epidemiologic characteristics. We are in urgent need of several comprehensive and effective control efforts to reverse this situation.

Reference intervals and factors contributing to serum cystatin C levels in a Chinese population.

Serum cystatin C (Cys‐C), an inhibitor of cysteine proteases, has been suggested as an ideal biomarker of glomerular filtration rate (GFR).