Genetic variants in IFIH1 and DDX58 influence hepatitis C virus clearance in Chinese Han population.

AIMS: To investigate the association between two RIG-I-like receptor gene polymorphisms and hepatitis C virus (HCV) infection in Chinese Han population. METHODS: The current study genotyped two selected SNPs (IFIH1 rs3747517 and DDX58 rs9695310) using TaqMan allelic discrimination assay to assess their association with the susceptibility and clinical outcome of HCV infection among 3065 participants (1545 non-HCV infection individuals, 568 spontaneous HCV clearance cases, and 952 persistent infection patients). RESULTS: IFIH1 rs3747517 (dominant model: Adjusted odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.07-1.68; P = 0.009) and DDX58 rs9695310 (dominant model: Adjusted OR = 1.43, 95% CI = 1.15-1.78; P = 0.001) were associated with chronic hepatitis C (CHC). And the risk of CHC increased when people were carrying more unfavorable rs3747517-GA/AA and rs9695310-GC/CC genotypes from zero to two with the chronic rates of 56.72%, 59.38%, and 69.01%, respectively (Ptrend < 0.001). CONCLUSION: Genetic variations at IFIH1 rs3747517 and DDX58 rs9695310 were independent predictors of chronic hepatitis C in Chinese Han population.

Impact of CYP2R1, CYP27A1 and CYP27B1 genetic polymorphisms controlling vitamin D metabolism on susceptibility to hepatitis C virus infection in a high-risk Chinese population.

CYP27A1, CYP2R1 and CYP27B1 hydroxylases are involved in the synthesis of 1, 25-hydroxyvitamin D3, which plays a role in the immune regulation and pathogenesis of hepatitis C virus (HCV) infection. The aim of the present study was to investigate the relationships between polymorphisms in vitamin D pathway genes and HCV infection outcomes in a Chinese population. Nine single-nucleotide polymorphisms (SNPs) of CYP27A1, CYP2R1 and CYP27B1 were genotyped in a high-risk Chinese population. The distributions of these SNPs were compared among groups with different outcomes of HCV infection, including 863 cases of persistent HCV infection, 524 cases of spontaneous clearance, and 1079 uninfected controls. The results showed that the CYP2R1 rs12794714-G, rs10741657-A, rs1562902-C, and rs10766197-G alleles were significantly associated with increased susceptibility to HCV infection (all PFDR < 0.05, in additive/dominant models), and the combined effect of the four unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 0.008). Moreover, haplotype analysis suggested that, compared with the most frequent haplotype (Ars12794714Grs10741657Trs1562902Ars10766197), the haplotype containing four unfavorable alleles, GACG, was associated with a higher risk of HCV infection. The results of our study suggest that genetic variants in CYP2R1 may be biomarkers for predicting the susceptibility to HCV infection in the Chinese population.

Genetic variations in vitamin D receptor were associated with the outcomes of hepatitis C virus infection among Chinese population.

Vitamin D has been considered as an immune modulator, and exerted the effect through the vitamin D receptor (VDR). This study investigated the associations of single-nucleotide polymorphisms (SNPs) of VDR with the outcomes of Hepatitis C virus (HCV) infection. Three SNPs (rs2228570, rs757343 and rs739837) were genotyped by TaqMan assay among Chinese population, including 538 HCV spontaneous clearance subjects, 834 persistent infection subjects and 1030 uninfected subjects. Binary logistic analyses were used to control the effects of confounding factors. The results showed that subjects with the rs757343 A allele and rs739837 A allele had the significantly reduced risk of HCV susceptibility (all PBonferroni<0.05 in dominant/additive model). In the stratified analysis, the protection of rs757343 A allele and rs739837 A allele against HCV infection remained effective in some subgroups. In addition, patients carrying rs739837 CA genotype were less prone to develop persistent infection (PBonferroni=0.033) and such effect still work in several subgroups in the stratified analysis. Furthermore, haplotype analysis indicated that when compared with the most frequent GC haplotype, the haplotype carrying AA (odds ratio (OR)=0.66, 95% confidence interval (CI)=0.56-0.78) and GA (OR=0.64, 95% CI=0.47-0.85) suggested a protective effect. Our findings indicated that the polymorphisms of VDR are associated with the outcomes of HCV infection among Chinese population.

Feasibility of Dual Flip Angle-Based Fast 3-Dimensional T1 Mapping for Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage of the Knee: A Histologically Controlled Study.

OBJECTIVE: The aim of the study was to validate dual-flip angle-based fast 3-dimensional (3D) T1 mapping for delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) by means of histological analyses in the assessment of the cartilage of the knee in a porcine model. METHODS: A total of 15 mini pigs were included in this study. The left knee anterior cruciate ligaments of all mini pigs were transected. The mini pigs were divided into 3 groups postoperatively, with 5 pigs randomly assigned to 1 group. Dual-flip angle-based fast T1 mapping for dGEMRIC was obtained in the sagittal planes at 0 week (group 1), 3 weeks (group 2), and 6 weeks (group 3) after operation, using an 8-channel knee coil. Magnetic resonance imaging was performed at 3T with dual-flip angle-based fast 3D T1 mapping sequence for morphological cartilage assessment of dGEMRIC T1 values. After MRI analysis, histological and biochemical composition (water, collagen, and glycosaminoglycan [GAG]) of the knee cartilage in the medial femoral condyle was quantified ex vivo. RESULTS: The T1 values obtained by the dual-flip angle-based fast 3D T1 mapping were positively correlated with the glycosaminoglycan content (r = 0.85; P < 0.05). The values had no significant correlation with the collagen content. The dGEMRIC-T1 values obtained by this method showed the medial femoral condyle cartilage in the anterior cruciate ligament-transected knee after transection decreased with time (P < 0.05). Histological sections of cartilage damage were correlated with MRI data. CONCLUSIONS: This study demonstrated the reliability of using dual-flip angle-based fast T1 mapping for dGEMRIC for the biochemical assessment of early cartilage degeneration. This technique is a powerful tool for researchers and clinicians to acquire sufficient resolution data within a reasonable scan time.

Epidemiology of Intermittent Exotropia in Preschool Children in China.

PURPOSE: To determine the prevalence, subtypes, and associated risk factors for intermittent exotropia (IXT) in preschool children aged 3 to 6 years in eastern China. METHODS: A population-based study including 5831 preschool children aged 3 to 6 years was conducted from 2011 to 2012 in Yuhua District, Nanjing, China, using an age-stratified random sampling procedure. Clinical examinations including ocular alignment, ocular motility, visual acuity, prism cover test, cycloplegia refraction, stereopsis screening, slitlamp examination, and fundus examination were performed by trained ophthalmologists and optometrists. Intermittent exotropia was defined as an acquired intermittent exodeviation of at least 10 prism diopters in an otherwise healthy child following the classification recommended by the National Eye Institute. RESULTS: The overall prevalence of IXT in this population was 3.24% (95% confidence interval, 2.79 to 3.69%), with no age (p = 0.19) and sex (p = 0.89) differences. Among 166 children with IXT, the "basic type" was the most common type of IXT (74.7%), the "divergence excess" was the second (19.9%), whereas the "convergence weakness" was the rarest (5.4%). In multivariate analysis adjusting for age, sex, and other confounders, the presence of IXT was only associated with a history of hypoxia at birth (odds ratio, 4.41; 95% confidence interval, 2.47 to 7.86). CONCLUSIONS: Intermittent exotropia affected approximately 1 in 30 Chinese preschool-aged children in eastern China, indicating a relatively higher burden of this pediatric eye condition in the world's most populous country. The presence of IXT was strongly associated with a history of hypoxia at birth.

Human Leukocyte Antigen Class II Alleles Are Associated with Hepatitis C Virus Natural Susceptibility in the Chinese Population.

Human leukocyte antigen (HLA) class II molecule influences host antigen presentation and anti-viral immune response. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) within HLA class II gene were associated with different clinical outcomes of hepatitis C virus (HCV) infection. Three HLA class II SNPs (rs3077, rs2395309 and rs2856718) were genotyped by TaqMan assay among Chinese population, including 350 persistent HCV infection patients, 194 spontaneous viral clearance subjects and 973 HCV-uninfected control subjects. After logistic regression analysis, the results indicated that the rs2856718 TC genotype was significantly associated with the protective effect of the HCV natural susceptibility (adjusted OR: 0.712, 95% CI: 0.554-0.914) when compared with reference TT genotype, and this remained significant after false discovery rate (FDR) correction (p = 0.024). Moreover, the protective effect of rs2856718 was observed in dominant genetic models (adjusted OR: 0.726, 95% CI: 0.574-0.920), and this remained significant after FDR correction (p = 0.024). In stratified analysis, a significant decreased risk was found in rs2856718C allele in the male subgroup (adjusted OR: 0.778, 95% CI: 0.627-0.966) and hemodialysis subgroup (adjusted OR: 0.713, 95% CI: 0.552-0.921). Our results indicated that the genetic variations of rs2856718 within the HLA-DQ gene are associated with the natural susceptibility to HCV infection among the Chinese population.

A dose-response meta-analysis of dietary lutein and zeaxanthin intake in relation to risk of age-related cataract.

BACKGROUND: Lutein and zeaxanthin are thought to have beneficial effects on protecting the lens against cataract formation, but findings from epidemiologic studies have been inconsistent. We aimed to conduct a meta-analysis of prospective cohort studies to examine the association between dietary lutein and zeaxanthin intake and risk of age-related cataract (ARC). METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library databases up to March 2013. Reference lists from retrieved articles were also reviewed. The adjusted relative risks (RRs) from each study were extracted to calculate a pooled estimate with its 95 % confidence interval (CI). The dose-response relationships were assessed by using generalized least-squares trend estimation. RESULTS: Six prospective cohort studies were identified involving 4,416 cases and 41,999 participants. For the comparison between the highest and the lowest categories of dietary lutein and zeaxanthin intake, significant inverse association were found for nuclear cataract (RR: 0.75; 95 % CI: 0.65, 0.85), but not for cortical cataract (RR: 0.85; 95 % CI: 0.53, 1.17) and for posterior subcapsular cataract (RR: 0.77; 95 % CI: 0.40, 1.13). Dose-response analysis showed that every 300 µg/d increment in dietary lutein and zeaxanthin intake was associated with a 3 %, 1 %, or 3 % reduction in the risk of nuclear cataract (RR: 0.97; 95 % CI: 0.94, 0.99), cortical cataract (RR: 0.99; 95 % CI: 0.95, 1.02), or posterior subcapsular cataract (RR: 0.97; 95 % CI: 0.93, 1.01) respectively. CONCLUSIONS: Dietary lutein and zeaxanthin intake is associated with a reduced risk of ARC, especially nuclear cataract in a dose-response manner, indicating a beneficial effect of lutein and zeaxanthin in ARC prevention.

Genetic variants of IFIH1 and DHX58 affect the chronicity of hepatitis C in the Chinese Han population.

Hepatitis C remains a major public health problem in the world. The host immune system plays a key role in viral clearance. This study aimed to investigate the connection between retinoic acid-inducible gene I-like (RIG-I-like) receptor gene polymorphism and hepatitis C chronicity in the Chinese Han population. The current study genotyped three SNPs (IFIH1 rs10930046 and DHX58 rs2074158, rs2074160) to assess their association with the chronicity of hepatitis C virus (HCV) infection among 1,590 participants (590 spontaneous HCV clearance cases and 1,000 persistent infection patients). Our research shows that DHX58 rs2074158-G allele (dominant model: adjusted OR = 1.53, 95% CI [1.20-1.95], P = 0.001; additive model: adjusted OR = 1.50, 95% CI [1.27-1.78], P < 0.001) and IFIH1 rs10930046-C allele (additive model: adjusted OR = 1.26, 95% CI [1.07-1.49], P = 0.005) were associated with chronic hepatitis C (CHC). And the risk of CHC increased in people carrying more unfavorable genotypes (rs2074158-AG/GG or rs10930046-CC), with the chronic rates for genotypes number from zero to two in 60.69%, 57.33%, and 85.93%, respectively (adjusted OR = 3.64, 95% CI [2.18-6.08]; P < 0.001). Genetic polymorphism of IFIH1 and DHX58 may be related to CHC in the Chinese Han population. Furthermore, the risk of CHC increases as the number of unfavorable genotypes carried by the HCV-infected person increases. IFIH1 rs10930046, DHX58 rs2074158, age, ALT, and AST levels were all independent predictors of CHC.

Identifying and Exploring the Candidate Susceptibility Genes of Cirrhosis Using the Multi-Tissue Transcriptome-Wide Association Study.

Objective: We identify and explore the candidate susceptibility genes for cirrhosis and their underlying biological mechanism. Methods: We downloaded the genome-wide association studies summary data of 901 cirrhosis cases and 451,363 controls and integrated them with reference models of five potential tissues from the Genotype-Tissue Expression (GTEx) Project, including whole blood, liver, pancreas, spleen, and thyroid, to identify genes whose expression is predicted to be associated with cirrhosis. Then, we downloaded gene expression data of individuals with hepatocellular carcinoma from TCGA database to conduct differential expression analysis to validate these identified genes and explored their possible role in driving cirrhosis via functional enrichment and gene set enrichment analysis (GSEA). Results: We identified 10 significant genes (SKIV2L, JPH4, UQCC2, RP11-91I8.3, MAU2, ERAP1, PUS3, ZNF677, ARHGAP40, and SHANK3) associated with cirrhosis at a Bonferroni-corrected threshold of p < 0.01, among which two (SKIV2L and JPH4) were identified in the liver and five (SKIV2L, JPH4, MAU2, SHANK3, and UQCC2) were validated by differential expression analysis at an FDR-corrected threshold of p < 0.01. The enrichment analysis showed that the degradation process of RNA, which is enriched by 58 genes, is significantly under-enriched in liver cancer tissues (p = 0.0268). Conclusion: We have identified several candidate genes for cirrhosis in multiple tissues and performed differential genetic analysis using the liver cancer database to verify the significant genes. We found that the genes SKIV2L and JPH4 identified in the liver are of particular concern. Finally, through enrichment analysis, we speculate that the process of mRNA transcription and RNA degradation may play a role in cirrhosis.

Genetic and hosts characterization of hantaviruses in port areas in Hainan Province, P. R. China.

BACKGROUND: Hantaviruses (HVs) are major zoonotic pathogens in China that cause hemorrhagic fever with renal syndrome (HFRS) posing a major threat to people's health. Hainan Province, an island located in Southeast China, is an ideal region for sea ports. The unique tropical monsoon climate in Hainan provides sufficient living conditions for rodents, which help spread HVs and other rodent-borne diseases. In the routine monitoring of hantavirus, there was no evidence that rodents in Hainan carried hantavirus. No patients infected with hantavirus were found in the past. However, the surveillance of HVs-carrying rodents covering the whole territory of Hainan has not stopped. METHODOLOGY/PRINCIPAL FINDINGS: For the monitoring of the prevalence of HVs in rodents and the search for theoretical reference for rodent control and HFRS prevention, a total of 60 rodents from 6 monitoring spots were trapped around main ports in Hainan between 2016 and 2019. HV positive samples were identified by a specific kit and sequenced. The data indicated that seven rodents (Rattus norvegicus) were positive for hantavirus with a positivity rate of 11.67%. Phylogenetic analysis suggested that the two complete sequence strains HN1 and HN4 in this research were highly similar to the sequence strains GZRn36 and GZRn148 isolated in Guangdong Province, and they located in the same phylogenetic tree branch which belongs to S2 subtype. Although the two partial sequences HT1 and HT2 isolated in Xisha Islands belong to S2 subtype according to the phylogenetic tree of L segment, they showed a great nucleotide difference with HN1 and HN4. We also found 13 amino acid variations compared with SEOV 80-39 and 6 amino acid mutations related to epitope, and the variations may reduce the effectiveness of the current HFRS vaccines used in humans. CONCLUSIONS/SIGNIFICANCE: The study indicated HVs carried by rodents found in Hainan Province may be transmitted from Guangdong Province through trading ports and carriage of goods by sea. So it is of great significance to strengthen the surveillance of rodents in port areas especially capture and eliminate rodents on ship. Timely elimination of host animals of hantavirus in port areas is necessary to prevent an outbreak of HVs disease.

Tumor necrosis factor-α promoter gene polymorphisms are not associated with hepatitis C virus infection in Chinese hemodialysis patients.

BACKGROUND AND AIMS: The aim of this study was to investigate the possible influence of tumor necrosis factor-α (TNF-α) gene promoter polymorphisms on the hepatitis C virus (HCV) infection in Chinese hemodialysis (HD) patients. METHODS: A total of 884 HD patients from 14 HD centers in south China were investigated. The TNF-α gene promoter polymorphisms at positions 238 and 308 of the patients were detected by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. RESULTS: Among the 884 patients, 176 (19.9%) were anti-HCV (+), and 142 (80.7%) of the anti-HCV (+) patients became chronically infected. The anti-HCV (+) patients showed longer duration of HD, higher rate of blood transfusion, kidney transplantation, and dialyzer reuse, compared with the anti-HCV (-) patients. However, the distributions of TNF-α -238 and -308 alleles and genotypes had no significant differences between the anti-HCV (+) and the anti-HCV (-) patients (p > 0.05). And the frequencies of the above alleles and genotypes were also approximately equally distributed in the persistent infection and in the viral clearance HD patients (p > 0.05). CONCLUSIONS: This study did not suggest that the TNF-α -238 and -308 polymorphisms had influence on the infection of HCV in Chinese HD patients.

[The application of time series analysis in predicting the influenza incidence and early warning].

OBJECTIVE: This research aimed to explore the application of ARIMA model of time series analysis in predicting influenza incidence and early warning in Jiangsu province and to provide scientific evidence for the prevention and control of influenza epidemic. METHODS: The database was created based on the data collected from monitoring sites in Jiangsu province from October 2005 to February 2010. The ARIMA model was constructed based on the number of weekly influenza-like illness (ILI) cases. Then the achieved ARIMA model was used to predict the number of influenza-like illness cases of March and April in 2010. RESULTS: The ARIMA model of the influenza-like illness cases was (1 + 0.785B(2))(1-B) ln X(t) = (1 + 0.622B(2))ε(t). Here B stands for back shift operator, t stands for time, X(t) stands for the number of weekly ILI cases and ε(t) stands for random error. The residual error with 16 lags was white noise and the Ljung-Box test statistic for the model was 5.087, giving a P-value of 0.995. The model fitted the data well. True values of influenza-like illness cases from March 2010 to April 2010 were within 95%CI of predicted values obtained from present model. CONCLUSION: The ARIMA model fits the trend of influenza-like illness in Jiangsu province.

Genetic Mutations in TNFSF11 Were Associated With the Chronicity of Hepatitis C Among Chinese Han Population.

Background: Recently, several studies have reported that the host immune response can be related to the RANKL/RANK/OPG signaling pathway. However, the associations of TNFSF11, TNFRSF11A, and TNFRSF11B gene polymorphisms in the RANKL/RANK/OPG pathway with hepatitis C virus (HCV) infection outcomes remain unclear. Methods: In this case-control study, 768 persistent HCV infection and 503 spontaneous HCV clearance cases, and 1,259 control subjects were included. The Taman-MGB probe method was utilized to detect TNFSF11 rs9525641, TNFRSF11A rs8686340, and TNFRSF11B rs2073618 genotypes. The distribution of three single nucleotide polymorphisms (SNPs) genotypes was analyzed using stata14.0. Results: SNPs rs9525641, rs8086340, and rs2073618 genotype frequencies followed the Hardy-Weinberg natural population equilibrium (p = 0.637, 0.250, and 0.113, respectively). Also, rs9525641 was significantly associated with HCV chronicity risk in recessive (OR = 1.203, 95% CI: 1.018-1.420, p = 0.030) and additive models (OR = 1.545, 95% CI: 1.150-2.075, p = 0.004). The stratified analysis showed that rs9525641 variant genotypes were associated with HCV chronicity among people older than 50 years (OR =1.562, 95% CI: 1.079-2.262, p = 0.018), females (OR = 1.667, 95% CI: 1.145-2.429, p = 0.008), ALT <40 U/L (OR = 1.532, 95% CI: 1.074-2.286, p = 0.018), and AST < 40 U/L (OR = 1.552, 95% CI: 1.095-2.201, p = 0.014). Conclusion: TNFRSF11 rs9525641 was significantly associated with HCV chronicity in the Chinese population.

[Estimation and prediction of the epidemic situation of acquired immunodeficiency syndrome in Jiangsu province].

OBJECTIVE: The aim of this study was to estimate and predict the AIDS epidemic situation in Jiangsu province by using a software named Estimation and Projection Package (EPP) and then to provide accurate information for making control plans and conducting interventions. METHODS: Date were obtained from the comprehensively monitored sentinels of AIDS and venereal diseases (Data were from 28 national monitored stations and 52 provincial stations. From 2003 to 2009, a total of 10 730 000 people had been monitored) as well as project survey and laboratory tests. EPP epidemic model was employed to analyze the prevalence and to predict future epidemic situations. RESULTS: A total of 830 000 and 1 020 000 people were monitored in 2003 and 2004 respectively, and 8 880 000 more people were monitored in the following 5 years. By the end of 2009, a total of 4103 HIV infection cases had been reported, among which 918 people were diagnosed with AIDS and 432 died. Since 2003, the cases infected through IDU had decreased from 66.84% (262/392) to 16.40% (142/868). However, the cases infected through sex contact had increased from 21.68% (85/392) to 77.40% (672/868). Among these cases, homosexual transmission and heterosexual transmission accounted for 39.10% (339/868) and 38.30% (333/868) respectively. It was estimated that there would be 14 290 HIV/AIDS cases in 2011 which is 18.10% (2191/12 099) higher than that in 2009. The estimated HIV infection rate would be 0.02%. CONCLUSION: EPP prediction showed the AIDS epidemic situation in Jiangsu province had an ascendant trend and the AIDS epidemic situation had demonstrated rapid growth. Therefore, it is necessary to take effective preventive measures to control the spread of AIDS.

[Psychological status in 1083 hospitalized patients with coronary artery disease].

OBJECTIVE: To explore the prevalence and associated factors of anxiety and depression symptoms in hospitalized Chinese patients with coronary artery disease (CAD). METHODS: From June 2007 to May 2009, 1083 hospitalized patients with confirmed coronary artery disease were recruited in this study. The ZUNG Self-rating Anxiety Scale (SAS) and the ZUNG Self-rating Depression Scale (SDS) were used for the psychological assessment. Economic status, living condition and the environment of both living and working places were evaluated by epidemiological questionnaires. RESULTS: The prevalence of pure anxiety, pure depression symptoms and the combination of anxiety and depression symptoms were 7.9%, 28.3% and 14.3% respectively. Incidence of anxiety and depression symptoms was significantly higher in female patients compared with in male patients (P = 0.003, 0.012 respectively) and in aged patients than in middle-aged patients (P = 0.001). The elderly, less than 9 years of education and poor sleep quality increased the risk of anxiety symptom with ORs of 1.63 (95%CI: 1.21 - 2.21), 1.54 (95%CI: 1.15 - 2.07) and 1.62 (95%CI: 1.34 - 1.96), respectively, while workplace noise, history of chronic disease and poor sleep quality increased the risk of depression symptom with ORs of 1.52 (95%CI: 1.18 - 1.98), 1.36 (95%CI: 1.06 - 1.75) and 1.27 (95%CI: 1.08 - 1.50), respectively. Female (OR = 1.91, 95%CI: 1.22-2.98), aged patient (OR = 1.84, 95%CI: 1.23 - 2.76), workplace noise (OR = 1.61, 95%CI: 1.07 - 2.42), history of chronic disease (OR = 1.84, 95%CI: 1.24 - 2.71) and poor sleep quality (OR = 1.73, 95%CI: 1.35 - 2.21) were significantly correlated with the combined incidence of anxiety and depression symptoms. CONCLUSION: Around half of the Chinese hospitalized CAD patients were complicated with various degrees of anxiety and/or depression symptoms. Female and aged patients were at higher risk for anxiety and depression symptoms. Sleep quality, workplace noise, years of education and history of chronic disease were independent risk factors for anxiety or depression symptoms.

Flavonoids intake and risk of lung cancer: a meta-analysis.

OBJECTIVE: A number of studies have evaluated the association between flavonoids intake and lung cancer risk. However, results were inconsistent. To clarify the role of flavonoids in lung cancer, we conducted a meta-analysis on this topic. METHODS: Two authors independently searched PubMed and EMBASE for studies regarding the association of flavonoids intake with lung cancer risk. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated by using random-effects model. RESULTS: Eight prospective studies and four case-control studies involving 5073 lung cancer cases and 237 981 non-cases were included in this meta-analysis. The combined results indicated a statistically significant association between highest flavonoids intake and reduced risk of developing lung cancer (RR = 0.76, 95% CI = 0.63-0.92). Furthermore, an increase in flavonoids intake of 20 mg/day was associated with a 10% decreased risk of developing lung cancer (RR = 0.90, 95% CI = 0.83-0.97). In stratified analyses, the highest flavonoids intake was significantly associated with decreased lung cancer risk in prospective studies, studies conducted in Finnish population, studies without adjustment for fruits and vegetables or vitamins, males, smokers and studies using dietary history interview for flavonoids intake estimation. Most subclasses of flavonoids were inversely associated with lung cancer except for hesperetin. CONCLUSIONS: Our data indicate that high or an increased intake of flavonoids is associated with reduced risk of lung cancer in some population but not in other population.

CYP24A1 genetic variants in the vitamin D metabolic pathway are involved in the outcomes of hepatitis C virus infection among high-risk Chinese population.

BACKGROUND AND AIMS: It has been demonstrated that 1,25-hydroxyvitamin-D3-24-hydroxylase, encoded by CYP24A1 gene, is a key enzyme that neutralizes the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in response to hepatitis C virus (HCV) infection. This study aimed to investigate whether CYP24A1 genetic variation is associated with HCV infection outcomes. METHODS: 848 HCV chronically infected subjects, 507 natural clearance subjects, and 1017 uninfected controls were enrolled. Nine single nucleotide polymorphisms (SNPs) in theCYP24A1 gene were genotyped using the Sequenom MassARRAY platform. RESULTS: After adjusting for age, gender, and routes of infection, logistic regression analyses showed that rs6013897-A was associated with an elevated risk of HCV infection (P<0.05). In addition, this study has also demonstrated that rs6068816-T significantly reduced the risk of chronic HCV infection, while rs3787557-C, rs6022999-G, and rs2248359-T significantly increased the risk of chronic HCV infection (all P<0.05). Haplotype analysis suggested that, compared to the most frequent Trs6068816Trs3787557Ars6022999Crs2248359 haplotype, the CTGT haplotype (adjusted OR=1.376, 95% CI=1.092-1.735, P=0.007) and CCAC haplotype (adjusted OR=1.483, 95% CI=1.139-1.929, P=0.003) were associated with an increased risk of chronic HCV infection. CONCLUSION: These findings indicate that SNPs in CYP24A1 gene may contribute to the risk of HCV infection and chronic HCV infection among a high-risk Chinese population.

The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population.

BACKGROUND AND AIM: To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C. METHODS: A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction-sequencing based typing (PCR-SBT). RESULTS: Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse. CONCLUSIONS: These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.

Genetic variation on the NFKB1 genes associates with the outcomes of HCV infection among Chinese Han population.

AIM: To investigate whether nuclear factor-kappa B1 (NFKB1) gene polymorphisms are associated with the outcomes of hepatitis C virus (HCV) infection in a Chinese high-risk population. METHODS: In this case-control study, 984 HCV-uninfected controls, 221 infected individuals with spontaneous HCV clearance, and 456 with persistent HCV infection were enrolled. Rs28362491 and rs72696119 were genotyped using the ABI TaqMan allelic discrimination assay. The functional annotation of the identified single nucleotide polymorphisms (SNPs) were further evaluated by bioinformatics analysis. RESULTS: Significant differences were observed among the three groups (P < 0.001) in terms of the frequency of rs28362491 SNP. In logistic regression analysis, rs28362491-ATTG deleted (D) was associated with a significantly increased risk of HCV infection compared to the major-type rs28362491-ATTG inserted (I) (dominant model: adjusted OR = 1.332, 95% CI = 1.059-1.674, P = 0.014; additive model: adjusted OR = 1.181, 95% CI = 1.021-1.367, P = 0.025), after adjusting for age, gender, and route of infection. Based on the in silico prediction, the RegulomeDB score for SNP rs28362491 was 3a, indicating that it can potentially regulate the transcription and expression of NFKB1 gene. CONCLUSION: NFKB1 rs28362491-D allele was functionally associated with the increased risk of susceptibility to HCV infection in the Chinese Han population.

Vitamin D binding protein polymorphisms influence susceptibility to hepatitis C virus infection in a high-risk Chinese population.

Vitamin D binding protein (VDBP) plays an important role in the immune modulation and pathogenesis of hepatitis C viral (HCV) infection by influencing serum vitamin D levels. The present study aims to evaluate the association of VDBP genetic polymorphisms with susceptibility to and chronicity of HCV infection in a high-risk Chinese population. Seven genetic variants in the VDBP gene were genotyped in a case-control study of 886 patients with HCV persistent infection, 539 subjects with spontaneous clearance, and 1081 uninfected controls. Logistic regression analysis was used to assess the effects of these variants on HCV infection outcomes. The results showed that two variants rs7041-G and rs3733359-T alleles were significantly associated with increased susceptibility of HCV infection, and the combined effect of the two unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 8.16 × 10-4). Interaction analysis manifested that rs7041-GT/GG and rs3733359-CT/TT jointly increased risk of HCV infection. Moreover, haplotype analysis suggested that compared with the most frequent TC haplotype, the haplotype carrying GT indicated a risk effect of HCV infection [odds ratio (OR) = 1.464]. However, no significant associations were observed for the other five variants. These findings implied that VDBP rs7041-G and rs3733359-T variants may contribute to increased susceptibility to HCV infection in a high-risk Chinese population.