Sijun Liu

Rapid Diagnosis of Drug Resistance to Fluoroquinolones, Amikacin, Capreomycin, Kanamycin and Ethambutol Using Genotype MTBDRsl Assay: A Meta-Analysis

Background There are urgent needs for rapid and accurate drug susceptibility testing of M. tuberculosis. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. In recent years, it has been evaluated in many settings, but with varied results. The aim of this meta-analysis was to synthesize the latest data on the diagnostic accuracy of GenoType MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol, in comparison with the phenotypic drug susceptibility test. Methods This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search terms of “MTBDRsl” and “tuberculosis” were used on PubMed, EMBASE, and Web of Science. QUADAS-2 was used to assess the quality of included studies. Data were analyzed by Meta-Disc 1.4. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and corresponding 95% confidence interval (CI) for each study. From these calculations, forest plots and summary receiver operating characteristic (SROC) curves were produced. Results Patient selection bias as well as flow and timing bias were observed in most studies. The summarized sensitivity (95% CI) was 0.874(0.845–0.899), 0.826(0.777–0.869), 0.820(0.772–0.862), 0.444(0.396–0.492), and 0.679(0.652–0.706) for fluoroquinolones, amikacin, capreomycin, kanamycin, and ethambutol, respectively. The specificity (95% CI) was 0.971(0.961–0.980), 0.995(0.987–0.998), 0.973(0.963–0.981), 0.993(0.985–0.997), and 0.799(0.773–0.823), respectively. The AUC (standard error) were 0.9754(0.0203), 0.9300(0.0598), 0.9885(0.0038), 0.9689(0.0359), and 0.6846(0.0550), respectively. Conclusion Genotype MTBDRsl showed good accuracy for detecting drug resistance to fluoroquinolones, amikacin and capreomycin, but it may not be an appropriate choice for kanamycin and ethambutol. The lack of data did not allow for proper evaluation of the test on clinical specimens. Further systematic assessment of diagnostic performance should be carried out on direct clinical samples.

Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis

Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics.

Prevalence, Awareness, Treatment and Control of Diabetes Mellitus in a Chinese Population.

Objective The purpose of this study is to evaluate the prevalence, awareness, treatment and glycemic control of diabetes mellitus (DM) in a Chinese population. The findings from this study are expected to offer scientific evidence to better prevent and control the growing number of reported and untreated cases. Methods A cross-sectional survey was conducted in Jiangsu, China. We recruited permanent residents over 18 years of age from eight towns in Jintan (JT) and six towns in Yangzhong (YZ) using a three-stage stratified cluster sampling method. The rates of DM prevalence, awareness, treatment and control as well as their related factors were analyzed. Results A total number of 15404 people were entered into the analysis. The DM prevalence, awareness, treatment and control rates were 7.31%, 58.35%, 51.87% and 14.12%, respectively. Multivariable logistic regression analysis showed that being female was positively related to prevalence (OR = 1.21, 95% CI: 1.07–1.37), awareness (OR = 1.52, 95% CI: 1.19–1.93), treatment (OR = 1.48, 95% CI: 1.17–1.88) and control (OR = 1.87, 95% CI: 1.30–2.67) of DM. Having a family history of diabetes was significantly correlated with DM risk (OR = 1.86, 95% CI: 1.37–2.54) and increased awareness (OR = 3.12, 95% CI: 2.19–4.47), treatment (OR = 3.47, 95% CI: 2.45–4.90) and control (OR = 1.81, 95% CI: 1.22–2.68) of DM. Former smoking status (OR = 1.82, 95% CI: 1.23–2.71), overweight (OR = 2.11, 95% CI: 1.72–2.60) and obesity (OR = 3.46, 95% CI: 2.67–4.50) were related to the risk of DM. Additionally, we found current drinking status to be positively correlated with DM risk (OR = 1.30, 95% CI: 1.01–1.66) and negatively correlated with DM awareness (OR = 0.41, 95% CI: 0.29–0.59) and treatment (OR = 0.41, 95% CI: 0.29–0.59). Our study highlights the high prevalence and inadequate awareness, treatment and control of DM in the Chinese population. Conclusions Management and prevention of DM-related complications should be considered an essential strategy by governments and society. This study assessed the reasons why DM has been increasing and established the first step in determining where to start regarding preventative methods.

Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese

BackgroundGenome-wide association study (GWAS) has identified that rs8050136 C/A polymorphism in fat mass and obesity-associated gene (FTO) was associated with the risk of type 2 diabetes (T2D) in Europeans. But this association was abolished after adjustment for body mass index (BMI), suggesting that the effect of rs8050136 on T2D risk might be mediated by BMI in Europeans. However, the findings in subsequent studies were inconsistent among Asian populations. To determine whether rs8050136 polymorphism in FTO is independently associated with the risk of T2D in Chinese, we conducted a case–control study with 2,925 T2D patients and 3,281 controls in Han Chinese.ResultsLogistic regression revealed that the A allele of rs8050136 was significantly associated with an increased risk of T2D, independent of BMI (odds ratio (OR) = 1.17, 95% confidence interval (95% CI) = 1.03-1.32, p = 0.016). Meta-analysis containing 10 reported studies and our data with a total of 15,819 cases and 18,314 controls further confirmed the association between rs8050136 polymorphism and T2D risk in East Asians (OR = 1.13, 95% CI = 1.07-1.19).ConclusionsOur findings indicate that the genetic variant in FTO may contribute to T2D risk in Han Chinese and rs8050136 polymorphism may be a genetic marker for T2D susceptibility.

Association study of CRP gene polymorphism and hypertension in Han Chinese population.

BACKGROUND Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT). METHODS A community-based case-control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes. RESULTS In stage 1, five SNPs had positive association with HT (P<0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T-C which was constructed by rs6677719 and rs10737175, haplotype T-T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥50years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population. CONCLUSIONS The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.

Genetic variants at 10q23.33 are associated with plasma lipid levels in a Chinese population

Plasma lipid abnormalities are implicated in the pathogenic process of type 2 diabetes. The IDE-KIF11-HHEX gene cluster on chromosome 10q23.33 has been identified as a susceptibility locus for type 2 diabetes. We hypothesized that genetic variants at 10q23.33 may be associated with plasma lipid concentrations. Seven tagging single nucleotide polymorphisms (SNPs: rs7923837, rs2488075, rs947591, rs11187146, rs5015480, rs4646957 and rs1111875) at 10q23.33 were genotyped in 3,281 subjects from a Han Chinese population, using the TaqMan OpenArray and Sequenom MassARRAY platforms. Multiple linear regression analyses showed that SNP rs7923837 in the 3′-flanking region of HHEX was significantly associated with triglyceride levels (P = 0.019, 0.031 mmol/L average decrease per minor G allele) and that rs2488075 and rs947591 in the downstream region of HHEX were significantly associated with total cholesterol levels (P = 0.041, 0.058 mmol/L average decrease per minor C allele and P = 0.018, 0.063 mmol/L average decrease per minor A allele, respectively). However, the other four SNPs (rs11187146, rs5015480, rs4646957 and rs1111875) were not significantly associated with any plasma lipid concentrations in this Chinese population. Our data suggest that genetic variants in the IDE-KIF11-HHEX gene cluster at 10q23.33 may partially explain the variation of plasma lipid levels in the Han Chinese population. Further studies are required to confirm these findings in other populations.

Evaluation of CpG-SNPs in miRNA promoters and risk of breast cancer

CpG-SNPs in gene promoter regions are proposed to be associated with multiple diseases. To date, few studies have focused on the associations between CpG-SNPs in miRNA promoters and the risk of breast cancer. In this study, 138 miRNAs differentially expressed between breast cancer and non-cancer tissues (fold change >2, P < 0.05) were identified using The Cancer Genome Atlas (TCGA) Research database. In total, 13 SNPs were selected in the promoters of the miRNAs and were evaluated in a case-control study of Chinese women including 1486 cases and 1519 controls. After multivariate logistic regression analysis, we found that three CpG-SNPs: rs1190983, rs155247, and rs62382272, were significantly associated with breast-cancer susceptibility in the population (Additive model: rs1190983: adjusted OR = 0.88, 95% CI: 0.79-0.99, P = 0.034; rs155247: adjusted OR = 0.83, 95% CI: 0.74-0.93, P = 0.002; rs62382272: adjusted OR = 1.24, 95% CI: 1.04-1.47, P = 0.016). eQTL analysis showed that these three SNPs were correlated with the expression of the related miRNAs in TCGA breast cancer tissues (P = 0.006,0.009,0.001 for rs1190983, rs155247, and rs62382272). Furthermore, rs1190983 was found to be associated with CpG site (cg20488673) methylation (meQTL) (P = 0.004), which was in turn correlated with miR-342 expression (P = 0.016). These findings indicated that the three CpG-SNPs in the promoters of miRNAs were likely to possess important biological functions to breast cancer in the Han Chinese population.

Genetic Variants in the Promoter Region of miR-10b and the Risk of Breast Cancer

Variants in microRNA genes may affect their expression by interfering with the microRNA maturation process and may substantially contribute to the risk of breast cancer. Recent studies have identified miR-10b as an interesting candidate because of its close association with the metastatic behavior of breast cancer. However, the roles of miR-10b-related single nucleotide polymorphisms in breast cancer susceptibility remain unclear. This case-control study evaluated the associations between variants in the upstream transcription regulation region of miR-10b and the risk of breast cancer among Chinese women. Seven potentially functional SNPs were investigated using genotyping assays. The potential biological functions of the identified positive SNPs were further evaluated using in silico databases. We found that rs4078756, which was located at the promoter region of miR-10b, was significantly associated with breast cancer risk (rs4078756 AG/GG versus AA, adjusted odds ratio: 1.17, 95% confidence interval: 1.02–1.35). The other six single nucleotide polymorphisms exhibited negative associations. Based on the in silico prediction, rs4078756 potentially regulated miR-10b expression through promoter activation or repression. These findings indicate that a potentially functional SNP (rs4078756) in the promoter region of miR-10b may contribute to breast cancer susceptibility among Chinese women.