Baohuan Zhang

A meta-analysis of interaction between Epstein-Barr virus and HLA-DRB1*1501 on risk of multiple sclerosis

Infection with Epstein-Barr virus (EBV) and HLA-DRB1*1501-positivity is a risk factor for multiple sclerosis (MS), but whether an interaction between these two factors causes MS is unclear. We therefore conducted a meta-analysis on the effect of the interaction between HLA-DRB1*1501 and EBV infection on MS. Searches of PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wanfan databases through February 2015 yielded 5 studies that met the criteria for inclusion in the meta-analysis. EBV infection and HLA-DRB1*1501-positivity were dichotomized. The additive (S) and multiplicative interaction indexes (OR) between EBV infection and HLA-DRB1*1501 and their 95% confidence intervals (95%CI) were calculated for each study and then combined in a meta-analysis. EBV infection was significantly associated with MS (OR = 2.60; 95%CI, 1.48–4.59). HLA-DRB1*1501 was associated with a significantly increased risk of MS (OR, 3.06; 95%CI, 2.30–4.08). An interaction effect between EBV infection and HLA-DRB1*1501 on MS was observed on the additive scale (S, 1.43; 95%CI, 1.05–1.95, P = 0.023), but no interaction effect was observed on the multiplicative scale (OR, 0.86, 95%CI, 0.59–1.26). This meta-analysis provides strong evidence that EBV alone, HLA-DRB1*1501 alone or their interaction is associated with an elevated risks of MS.

Association of polymorphisms in the MyD88, IRAK4 and TRAF6 genes and susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a southern Han Chinese population.

Type 2 diabetes mellitus (T2DM) has been linked to a state of low-grade inflammation resulting from abnormalities in the innate immune pathway. MyD88 is an essential adaptor protein for TLR signaling, which is involved in activating NF-κB through IRAK4 and TRAF6. To investigate the effects of the MyD88, IRAK4 and TRAF6 polymorphisms in the susceptibility of T2DM and diabetic vascular complications, eight SNPs were analyzed in 553 T2DM patients and 553 matched healthy controls. Gene-gene interactions and haplotype associations were also evaluated. We found a significant increased risk of T2DM for the AG genotype of rs6853 in MyD88 gene and the CT genotype of rs4251532 in IRAK4 gene. Significant association was also found between rs16928973 in TRAF6 gene and diabetic nephropathy (DN) under the allelic model. Moreover, the TA haplotype in TRAF6 was negatively associated with DN. No significant gene-gene interactions were found. In conclusion, our results indicate that the polymorphisms in TLR-MyD88-NF-κB signaling pathway confer genetic susceptibility to T2DM and DN.

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.

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

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.

Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis

Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22–1.30) and 1.17 (95% CI: 1.14–1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.

The association between Toxoplasma gondii infection and hypertensive disorders in T2DM patients: a case-control study in the Han Chinese population

Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of infection with Toxoplasma gondii (T. gondii) is more than one-third of the total world population. The effects of T. gondii infection on the risk of diabetic complications and comorbidities are unclear. This study aims to determine the relationship between T. gondii infection and complications of T2DM in the Han Chinese population. We collected 1580 blood samples from T2DM patients and measured the levels of specific IgG antibodies against T. gondii in the sera of these patients using an ELISA assay. A logistic regression analysis was performed to estimate the effect of T. gondii infection on the complications of T2DM, while adjusting for age, gender, and triglyceride level (TG). We applied the multifactor dimensionality reduction (MDR) method to detect the interactions between T. gondii infections, demographic indexes and biochemical indicators among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI =0.45–0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45–0.89, P = 0.009) were influencing factors in T. gondii infections. T2DM patients who were infected with T. gondii had a 2.34 times risk of developing hypertension than those patients without T. gondii infection (OR = 2.34, 95%CI = 1.12–4.88, P = 0.024). The multiplicative interaction analysis and the additive interaction analysis did not reveal any evidence of interactive effects on diabetic complications and comorbidities. T. gondii might be a factor associated with hypertension in T2DM patients.

Association Between SLC30A8 rs13266634 Polymorphism and Risk of T2DM and IGR in Chinese Population: A Systematic Review and Meta-Analysis

Introduction: Published data regarding the association between solute carrier family 30, member 8 (SLC30A8) rs13266634 polymorphism and type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) risks in Chinese population are in-consistent. The purpose of this meta-analysis was to evaluate the association between SLC30A8 rs13266634 and T2DM/IGR in a Chinese population. Material and Methods: Three English (PubMed, Embase, and Web of Science) and three Chinese databases (Wanfang, CNKI, and CBMD database) were used for searching articles from January 2005 to January 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated with the random-effect model. Trial sequential analysis was also utilized. Results: Twenty-eight case-control studies with 25,912 cases and 26,975 controls were included for SLC30A8 and T2DM. Pooled risk allele C frequency for rs13266634 was 60.6% (95%CI: 59.2–62.0%) in the T2DM group and 54.8% (95%CI: 53.2–56.4%) in the control group which had estimated OR of 1.23 (95%CI: 1.17–1.28). Individuals who carried major homozygous CC and heterozygous CT genotype were at 1.51 and 1.23 times higher risk of T2DM, respectively, than those carrying minor homozygous TT. The most appropriate genetic analysis model was the co-dominant model based on comparison of OR1, OR2 and OR3. Five articles that involved 4,627 cases and 6,166 controls were included for SLC30A8 and IGR. However, no association was found between SLC30A8 rs13266634 and IGR (C vs. T, OR = 1.13, 95%CI: 0.98–1.30, p = 0.082). TSA revealed that the pooled sample sizes of T2DM exceeded the estimated required information size but not the IGR. Conclusion: The present meta-analysis demonstrated that SLC30A8 rs13266634 was a potential risk factor for T2DM, and more studies should be performed to confirm the association between rs13266634 polymorphism and IGR.

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.