Qiuyan Wang

High serum ferritin level is an independent risk factor for metabolic syndrome in a Chinese male cohort population

BackgroundElevated serum ferritin levels have been reported to contribute to metabolic syndrome (MetS). We examined the association of serum ferritin levels with the development of MetS in a representative sample of Chinese male adult population.MethodThe data came from the 2009–2013 Fangchenggang Area Males Health and Examination Survey (FAMHES). We combined a cross-sectional study of 2417 males and a longitudinal study of 857 males who participated in the FAMHES.ResultThe serum ferritin level of MetS was higher than that of nonMetS (median and percentiles 25–75: 447.4 (294.1-612.4) vs. 302.4 (215.0-435.8) ng/ml, p < 0.01). A positive correlation between ferritin concentrations and blood pressure (Systolic BP: R = 0.110, Diastolic BP: R = 0.158), waist circumference (R = 0.333), fasting glucose (R = 0.089), triglyceride (R = 0.315) and low high-density lipoprotein cholesterol (R = 0.130) was significant (all p < 0.001). Compared with the level of ferritin in the group with no MetS component, the group with all five MetS components had a higher ferritin level (554.7 (340.1-606.4) vs. 274.2 (198.2-384.4) ng/ml). The odd radio (OR) was higher for MetS in the highest ferritin quartile (OR = 2.29, 95% CI = 1.47-3.54) compared with the lowest ferritin quartile after adjustment for multi-factors. After 4-year follow up, 79 subjects newly diagnosed with MetS in 857 cohort male participants in 2013. Compared with the lowest ferritin quartile, the RR of the highest ferritin quartile was 2.55 (95% CI = 1.30-5.00) after multiple adjustments (p < 0.01).ConclusionOur findings confirm that the serum ferritin level is associated with the independent components of MetS, and elevated ferritin level is an independent risk factor for MetS development in the Chinese male population during the 4-year follow-up period.

Low Serum Sex Hormone-Binding Globulin Associated with Insulin Resistance in Men with Nonalcoholic Fatty Liver Disease

The presence of nonalcoholic fatty liver disease (NAFLD) is a strong risk predictor for type 2 diabetes (T2D). A reduction in sex hormone-binding globulin (SHBG) is associated with NAFLD. Low SHBG is also associated with insulin resistance (IR). However, very limited data are available for the association of SHBG and IR in patients with NAFLD. The study aims to clarify the association between SHBG and IR in patients with NAFLD. In this cross-sectional study, 334 men with NAFLD were recruited. SHBG, total testosterone, free testosterone, total cholesterol, triglyceride, insulin, and glucose concentrations were measured. Homeostatic model assessment (HOMA)-IR and HOMA-β were calculated. Spearmans correlations and multiple linear regressions were used to analyze the association between SHBG and IR. Men with moderate-severe NAFLD had higher waist circumference, BMI, total cholesterol, triglyceride, insulin, HOMA-IR, HOMA-β, and free testosterone, but lower SHBG than the mild NAFLD. The moderate-severe NAFLD group exhibited higher HOMA-IR (2.38±1.35 vs. 4.16±2.84, p<0.001) and lower SHBG (25.89±11.89 vs. 30.13±12.97 nmol/l, p<0.001) than the other group. SHBG value was negatively correlated with insulin, and HOMA-IR, but was not significantly correlated with glucose and testosterone. The multiple linear regression analysis showed that SHBG was significantly associated with insulin (β=- 0.241, p<0.001), and HOMA-IR (β=- 0.229, p<0.001), even adjusting for potential confounders. In conclusion, low serum SHBG is associated with IR in men with NAFLD.

Comprehensive investigation of aberrant microRNA profiling in bladder cancer tissues.

There has been accumulative evidence that microRNAs (miRNAs) play essential roles in the tumorigenesis and progression of bladder cancer. However, individual studies and small sample size caused discrepant outcomes. Thus, the current study focused on a comprehensive profiling of all differentially expressed miRNAs in a total of 519 bladder cancer tissue samples, based on miRNA microarray data. Altogether, 11 prioritized miRNAs stated by 21 published microarray datasets, including five down-regulated (miR-133a-3p, miR-1-3p, miR-99a-5p, miR-490-5p, and miR-133b) and six up-regulated candidate miRNAs (miR-182-5p, miR-935, miR-518e-3p, miR-573, miR-100-3p, and miR-3171) were analyzed with vote-counting strategy and a Robust Rank Aggregation method. Subsequently, miRNA in silico target prediction and potential pathway enrichment analysis were performed to investigate the prospective molecular mechanism of miRNAs in the tumorigenesis of bladder cancer. We found that most of the relative pathways of the aberrantly expressed miRNAs found in the current study were closely correlated with different biological processes, cellular components, molecular functions, cancer pathogeneses, and some cell signalings, such as Wnt signaling, insulin/IGF, PI3 kinase, and FGF signaling pathways. Hence, a comprehensive overview on the miRNA expression pattern in bladder cancer tissues was gained by the current study. These miRNAs might be involved in the tumorigenesis and deterioration of bladder cancer.

16S rRNA gene sequencing reveals altered composition of gut microbiota in individuals with kidney stones

Nephrolithiasis is a common urological disease with high prevalence and recurrence rates. Characterizing gut microbiome profiles of nephrolithiasis patients may provide valuable insights and potential biomarkers for the disease. Therefore, we explored the relation between gut microbiome and nephrolithiasis using 16S ribosomal RNA (rRNA) gene sequencing. 13 patients with multiple kidney stones and 13 matched healthy controls were recruited. A decreasing trend in number of observed species in nephrolithiasis patients was detected, although statistical significance was not reached (p = 0.086). The inter-group variability in community structure by beta diversity analysis showed a clear separation between nephrolithiasis patients and healthy controls. Twenty genera differentiated significantly in relative abundance between nephrolithiasis patients and healthy controls (all p < 0.05). Among the 20 genera, Phascolarctobacterium, Parasutterella, Ruminiclostridium_5, Erysipelatoclostridium, Fusicatenibacter and Dorea were correlated with the concentration of the trace elements in blood, including potassium, sodium, calcium and chlorinum. Characteristic microbiome in nephrolithiasis patients was also identified by linear discriminant analysis effect size (LEfSe). These findings may provide novel and non-invasive potential diagnostic biomarkers for nephrolithiasis, and contribute to prevention and treatment of nephrolithiasis from the perspective of maintaining micro-ecological equilibrium in gut.

Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis.

Introduction Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression. Materials and methods We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA–gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA. Results Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)–receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA–gene network. Conclusion These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.

Breast cancer in postmenopausal women is associated with an altered gut metagenome

BackgroundIncreasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically.MethodsWe performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls.ResultsMicrobial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation.ConclusionThe composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.

Significant association between RGS14 rs12654812 and nephrolithiasis risk among Guangxi population in China

Nephrolithiasis is a worldwide health problem that affects almost all populations. This study aimed to evaluate the association between rs12654812 of regulator of G protein signaling 14 (RGS14) gene and nephrolithiasis in the Chinese population.

HIPK2 polymorphisms rs2058265, rs6464214, and rs7456421 were associated with kidney stone disease in Chinese males not females

BACKGROUND AND AIM Recent studies have shown that genetic factors are involved in the development of kidney stone disease (KSD). A case-control association analysis was performed to investigate the association between homeodomain-interacting protein kinase 2 (HIPK2; OMIM *606868) polymorphisms and KSD. METHODS A total of 890 KSD patients and 920 healthy subjects were analyzed. Polymorphisms were genotyped using SNPscanTM high-throughput SNP classification technology. The genotypic and allelic frequencies in KSD patients and healthy individuals were analyzed using a Chi-square test. RESULTS The genotype and allele distributions of the three polymorphisms (rs2058265, rs6464214, and rs7456421 in HIPK2) displayed strong associations with KSD in males (rs2058265: odds ratio [OR] 2.480,95%confidence interval [CI] 1.205-5.106, p = 0.014; rs6464214: OR 2.466, 95%CI 1.198-5.078, p = 0.014; rs7456421: OR 2.846, 95%CI 1.362-5.947, p = 0.005; perallele: r2058265T, OR 1.357, 95%CI 1.073-1.715, p = 0.011; rs6464214G, OR 1.340, 95%CI 1.060-1.693, p = 0.014; rs7456421C, OR 1.356, 95%CI 1.073-1.713, p = 0.011). Patients carrying the T allele of rs2058265, the G allele of rs6464214, or the C allele of rs7456421 showed higher systolic blood pressure, creatinine, and uric acid levels compared with wild-genotype individuals after adjusting for age, gender, and body mass index (p < 0.005). CONCLUSION The association of HIPK2 gene polymorphisms with KSD was only observed in males but not in females. HIPK2 gene polymorphisms were also involved in the changes of KSD-related metabolic traits.

Identification of three novel loci of ALDH2 Gene for Serum Folate levels in a Male Chinese Population by Genome-Wide Association Study

BACKGROUND Serum folate is important in clinical researches and DNA synthesis and methylation. Some loci and genes that are associated with folate levels had been detected by genome-wide association studies (GWAS), such as rs1801133 in MTHFR and rs1979277 in SHMT1. Nevertheless, only a small part of variants has been clearly identified for serum folate. Hence, we conducted a GWAS to discover new inherited susceptibility and gene-environment interactions on serum folate concentration. MATERIALS AND METHODS In a healthy Chinese population of 1999 men, genotyping was performed using Illumina HumanOmni1-Quad BeadChip. Serum folate levels were measured by enzyme-linked immunosorbent assay (ELISA), pathway enrichment analysis and statistical analysis were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Statistic Package for Social Science (SPSS). RESULTS We validated that rs1801133 in MTHFR was significantly involved in serum folate (P = 4.21 × 10-19). Surprisingly, we discovered three novel loci rs3782886, rs671, and rs4646776 of ALDH2 gene were suggestively significantly associated with folate serum folate levels in the male population studied (P = 2.17 × 10-7, P = 3.60 × 10-7, P = 3.99 × 10-7, respectively) after adjusting for population stratification, BMI and age. Men with the AA genotype had significantly higher serum folate levels compared with men with the GG/AG genotype. But we found ALDH2 gene mutation no relation to part of environmental factors on serum folate levels. CONCLUSION In a male Chinese population, genome-wide association study discovered that three novel SNPs rs3782886, rs671 and rs4646776 of ALDH2 gene were suggestively significantly associated with serum folate levels.

Cross-sectional and longitudinal associations between serum testosterone concentrations and hypertension: Results from the Fangchenggang Area Male Health and Examination Survey in China

BACKGROUND Low testosterone concentrations have been suggested as a risk factor for hypertension, but their contribution to the development of hypertension is not well studied. We carried out a cohort study based on the results of an earlier cross-sectional investigation. We established the association between testosterone concentrations and hypertension. METHOD Data on 2427 healthy male subjects, aged from 17 to 88 y, were collected for the cross-sectional study. A representative sample of 853 individuals who did not suffer from hypertension at baseline was followed up for 4 y. Differences between the tertiles groups of sex hormones were analyzed, relative risks (RR) were estimated using binary logistic regression model. RESULTS In the cross-sectional analysis, the serum total testosterone (TT), free testosterone (FT), and bioavailable testosterone (BT) concentrations of the hypertensive population were lower than those of the non-hypertensive population. Binary logistic regression analysis showed that TT, BT, and FT were inversely associated with hypertension. Moreover, decreasing odds ratio (OR) was observed from the lowest tertile group to the highest tertile group. After multivariate adjustment, the correlation between FT, BT, and hypertension was attenuated. Statistically significant differences remained only in the middle tertile group of TT and in the highest tertile group of TT, FT, and BT. In the longitudinal analysis, the 4-y incidence of hypertension was higher in participants with lower TT than in those with higher TT. Subjects in the middle and highest tertile groups of TT had an RR of 0.35 (0.22-0.57) and 0.30 (0.18-0.50), respectively (P for trend <0.001). After further adjustments, these associations still remained statistically significant. CONCLUSIONS Serum TT, FT, and BT concentrations were inversely associated with blood pressure in man, and TT independent of age and body mass index (BMI) influences the development of hypertension. Furthermore, TT can be employed as a risk marker for hypertension in the identification of high-risk individuals.