Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population.

Human papillomavirus (HPV) infection is a definite risk factor for cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The cGAS-STING pathway in innate immunity plays an important role in protecting against HPV infection. Chen et al. described that the rs2516448 SNP in the MHC locus may affect susceptibility to cervical cancer, a finding that we attempted to replicate in a Chinese population. To investigate the effects of cGAS, STING and MHC polymorphisms on susceptibility to cervical precancerous lesions, 9 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions were also evaluated. We found a significantly decreased risk of cervical precancerous lesions for the GG genotype of rs311678 in the cGAS gene (ORadjusted = 0.40, 95% CI: 0.16-0.98). Moreover, MDR analysis identified a significant three-locus interaction model, involving HPV infection, age at menarche and rs311678 in cGAS. Additionally, a significant antagonistic interaction between HPV infection and rs311678 was found on an additive scale. In conclusion, our results indicate that the rs311678 polymorphism in the cGAS gene confers genetic susceptibility to cervical precancerous lesions. Moreover, the three-way gene-environment interactions further demonstrate that the rs311678 polymorphism in cGAS can significantly decrease the risk of HPV infection and the elder at menarche.

Meta-Analysis on Associations of RGS1 and IL12A Polymorphisms with Celiac Disease Risk.

The pathogenesis of celiac disease (CD) has been related to polymorphisms in the regulator of G-protein signaling 1 (RGS1) and interleukin-12 A (IL12A) genes, but the existing findings are inconsistent. Our aim is to investigate the associations of two single-nucleotide polymorphisms (SNPs) (rs2816316 in RGS1 and rs17810546 in IL12A) with CD risk using meta-analysis. We searched PubMed and Web of Science on RGS1 rs2816316 and IL12A rs17810546 with CD risk. Odds ratio (OR) and 95% confidence interval (CI) of each SNP were estimated. All statistical analyses were performed on Stata 12.0. A total of seven studies were retrieved and analyzed. The available data indicated the minor allele C of rs2816316 was negatively associated with CD (C vs. A: OR = 0.77, 95% CI = 0.74-0.80), and a positive association was found for the minor allele G of rs17810546 (G vs. A: OR = 1.37, 95% CI = 1.31-1.43). The co-dominant model of genotype effect confirmed the significant associations between RGS1 rs2816316/IL12A rs17810546 and CD. No evidence of publication bias was observed. Our meta-analysis supports the associations of RGS1 and IL12A with CD and strongly calls for further studies to better understand the roles of RGS1 and IL12A in the pathogenesis of CD.

Insulin gene VNTR polymorphisms -2221MspI and -23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis.

AIMS: A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive. METHODS: We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls. RESULTS: For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of -23HphI on LADA. CONCLUSIONS: Our results support the existence of associations of INS with T1D and LADA.

Systematic review and meta-analysis of the association between IL18RAP rs917997 and CCR3 rs6441961 polymorphisms with celiac disease risks.

OBJECTIVES: We performed a systematic review and meta-analysis to estimate the polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility. METHODS: PubMed and Web of Science databases were searched (to June 2015) on IL18RAP rs917997 and CCR3 rs6441961 polymorphisms. RESULTS: The meta-analysis included 16 and 7 studies for rs917997 and rs6441961, respectively. The minor risk A allele at both rs917997 and rs6441961 carried risks (odds ratios) of 1.24 (95% CI 1.18-1.31) and 1.21 (95% CI 1.12-1.31), respectively. These alleles contributed to increase risks in all celiac disease patients by 5.04 and 6.35%. The estimated lambdas were 0.73 and 0.51, suggesting that an additive model would be the best choice for both gene effects. CONCLUSIONS: This meta-analysis provides robust estimates that IL18RAP rs917997 and CCR3 rs6441961 are potential risk factors for celiac disease in European populations. Studies are needed to confirm these findings in different ethnicities.

Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta-analysis.

OBJECTIVE: The meta-analysis was to determine the diagnostic value of the combining tests for Down syndrome and to evaluate their utilities in the Down syndrome screening. METHOD: Through comprehensive literature search, 24 studies met the inclusion criteria and were included in the databases (PubMed, Wed of knowledge, Chinese National Knowledge Infrastructure (CNKI)). Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The summary receiver operating characteristic curve was also undertaken. RESULTS: The overall sensitivity and specificity of the combination of NT and free ß-hCG and PAPP-A for Down syndrome were 0.86(95%CI 0.75-0.92) and 0.96(95%CI 0.95-0.97), respectively. The summary positive likelihood ratio and negative likelihood ratio were 23.3 (95%CI 16.7-32.5) and 0.15(95%CI 0.08-0.26), respectively. The pooled diagnostic odds ratio was 156 (95%CI 75-326). CONCLUSION: The meta-analysis shows the accumulative evidence for the clinician that the performance of the combined test of MA and NB and NT and PAPP-A and free ß-hCG is the most effective test in the four different combined tests, while, the combination of NT and PAPP-A and free ß-hCG is a cost-effective screening tool for Down syndrome.

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study.

BACKGROUND: It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China METHODS: 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. RESULTS: Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. CONCLUSIONS: HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China.

The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis.

Although the polymorphisms of PTPN22 and the variants of CTLA-4 have been reported to be the susceptibility genes, which increased risk of latent autoimmune diabetes in adults (LADA), the results remained inconclusive. The aim of this meta-analysis was to evaluate the association between the polymorphisms of two genes and LADA. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. Data from ten studies published between 2001 and 2013 were pooled for two polymorphisms: rs2476601 in the PTPN22 gene and rs231775 in the CTLA-4 gene. Data extraction and assessments for risk of bias were independently performed by two reviewers. Fixed-effect model and random-effect model were used to pool the odds ratios; meanwhile, heterogeneity test, publication bias and sensitive analysis were explored. The minor T allele at rs2476601 and the minor G at rs231775 carried estimated relative risks (odds ratio) of 1.52 (95 % CI 1.29-1.79) and 1.39 (95 % CI 1.11-1.74), respectively. These alleles contributed to an absolute lowering of the risk of all LADA by 4.88 and 14.93 % when individuals do not carry these alleles. The estimated lambdas were 0.49 and 0.63, suggesting a codominant model of effects was most likely for two genes. In summary, our systematic review has demonstrated that PTPN22 rs2476601 and CTLA-4 rs231775 are potential risk factors for LADA. An updated meta-analysis is required when more studies are published to increase the power of these polymorphisms and LADA.

Antiviral activity of polymethoxylated flavones from "Guangchenpi", the edible and medicinal pericarps of citrus reticulata 'Chachi'.

The present study found that the supercritical fluid extract of "Guangchenpi" possessed in vitro antiviral activity against respiratory syncytial virus (RSV). Bioassay-guided isolation and identification of this extract led to obtain five active polymethoxylated flavones (1-5). Cytopathic effect (CPE) reduction assay exhibited that tangeretin (2) and nobiletin (3), two major polymethoxylated flavones in the extract, possessed better anti-RSV effect comparable to the positive control ribavirin. Plaque reduction assay revealed that tangeretin dose-dependently inhibited RSV-induced plaque formation on the HEp-2 cells. This polymethoxylated flavone mainly affected the intracellular replication of RSV, and it also could inhibit RSV entry into the HEp-2 cells. Further investigations with quantitative real-time PCR and confocal and Western blot assays indicated that tangeretin downregulated the expression of RSV phosphoprotein (P protein). Results suggest the potential application of the supercritical fluid extract of "Guangchenpi" and tangeretin in the treatment and the prevention of RSV infection.

Prevalence of human papillomavirus infection in Guangdong Province, China: a population-based survey of 78,355 women.

BACKGROUND: The prevalence of human papillomavirus (HPV) infection and the distribution of different HPV genotypes vary greatly within different geographical and ethnic populations, especially in Asia. The HPV infection data based on regional population are extremely important for researchers to develop new efficient HPV screening assays and estimate the effect of vaccines on preventing from cervical cancer. METHODS: A total of 78,355 women from Guangdong Province, China, whose ages were from 18 to 75 years were enrolled in this study. All epidemiological data were obtained by face-to-face interview. Cervical exfoliated cells were collected, and HPV-DNA test was conducted with the matrix-assisted laser desorption/ionization time-of flight mass spectrometry. RESULTS: The overall HPV infection prevalence in the study population was 7.3%. The top 6 HPV genotypes were HPV16 (1.5%), HPV52 (1.2%), HPV58 (1.0%), HPV18 (0.7%), HPV45 (0.5%), and HPV6 (0.5%), accounting for 69.7% of all detected HPV infection types. Two peaks of HPV infection were detected in the population of old age group (>50; 9.6%) and young group (<25; 8.2%). Infection with single genotype HPV (6.2% in all; 85.7% in HPV-positive women) was more frequent than infection with multiple HPV (1.0% and 14.3% respectively). Results of multivariate logistic regression revealed that sexual active years, numbers of sexual partner, and numbers of pregnancy were risk factors of HPV infection. CONCLUSIONS: This study provides useful epidemiological information on cervical HPV infection prevalence in general female population from Guangdong Province, China. In this population, HPV infection prevalence was 7.3%, and genotypes HPV16, HPV52, and HPV58 showed a relatively high prevalence.