Fei-fei Han

The Effect of CHEK2 Variant I157T on Cancer Susceptibility: Evidence from a Meta-Analysis

Cell cycle checkpoint kinase 2 (CHEK2) is a checkpoint kinase that plays an important role in the DNA damage signaling network. Numerous epidemiological studies have evaluated the association between the CHEK2 I157T variant and cancer susceptibility. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CHEK2 I157T variant is associated with cancer susceptibility. PubMed, Embase (before 2012-10-1), Google Scholar, and CBMdisc were searched for studies on the relationship of the CHEK2 I157T variant and the incidence of cancer. Eligible articles were included for data extraction. The main outcome was the frequency of CHEK2 I157T polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. In total, 26,336 cases and 44,219 controls from 18 case-control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19-1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42-1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24-2.26, p=0.0008). We also found an association of the CHEK2 I157T variant with familial cases (OR=1.85, 95% CI=1.51-2.26, p<0.00001). However, the association was not established for other types of cancer (OR=1.09, 95% CI=0.75-1.57, p=0.66). This meta-analysis demonstrates that the CHEK2 I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.

Association of tissue plasminogen activator and plasminogen activator inhibitor polymorphism with myocardial infarction: A meta-analysis

INTRODUCTION To investigate whether t-PA Alu repeat insertion/deletion (I/D) and PAI-1 4G/5G genetic variations are associated with the risk of MI. METHODS We conducted a meta-analysis to assess the association between the t-PA I/D and PAI-1 4G/5G polymorphisms and risk of MI. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African), gender and age. Forty one eligible studies including 12,461 cases and 14,993 controls were identified to evaluate the impact of PAI-1 4G/5G polymorphism on MI. Seven studies investigated the relationship between t-PA I/D and MI. RESULTS This meta-analysis revealed that the PAI-1 4G allele (4G/4G and 4G/5G genotype) was associated with an increased risk of MI compared with the 5G allele in the overall population (OR=1.094, 95% CI=1.021 - 1.172, p=0.011). The relative risks of MI for 4G/4G genotype was increased when compared to 5G/5G genotype and 5G allele, with odds ratio at 1.157 (95% CI 1.015 - 1.320, p=0.029) and 1.126 (95% CI =1.015 - 1.249, p=0.025). However, the results show that the 4G/5G polymorphism risk for MI was not associated with ethnicity stratification as Caucasian, Asian or African population. No substantial differences in the genotype distributions were observed in the MI group and control group along the lines of gender and age. After multivariable analysis t-PA I/D polymorphism showed no consistent association with MI. CONCLUSIONS This study suggests that the 4G/5G polymorphism of PAI-1 may be a risk factor for MI in overall populations.

Genetic risk factors for glucocorticoid-induced osteonecrosis: A meta-analysis

Glucocorticoid-induced osteonecrosis is a common and severe adverse event. We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis. Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1). The meta-analysis revealed that the PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR=1.932, 95% CI=1.145-3.261). The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3.217 (95% CI 1.667-6.209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2.304 (95% CI=1.235-4.299) and 2.307 (95% CI=1.527-3.485) in combined studies, respectively. The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1.668, 95% CI=1.214-2.293) and TT genotype (OR 2.946, 95% CI=1.422-6.101). There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis. Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis.

Association between co-stimulatory molecule gene polymorphism and acute rejection of allograft

Co-stimulatory molecules play important roles in T cell-mediated immune response and transplantation. Numerous epidemiological studies have evaluated the association between CD28, CTLA-4 gene variant and allograft rejection. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CD28 IVS3 +17T/C variant, CTLA-4, CD86 and PDCD1 gene polymorphisms were associated with allograft rejection susceptibility. PubMed and Embase (before 2014-3-25), were searched for studies on the relationship of CD28, CTLA-4, CD86 and PDCD1 gene polymorphisms and the incidence of allograft rejection susceptibility. Eligible articles were included for data extraction. The main outcome was the frequency of co-stimulate molecule gene polymorphisms between rejection and non-rejection populations. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Significant associations of the CD28 IVS3 +17T/C variant with acute allograft rejection susceptibility were found (CC +CT/TT OR, 1.45; 95% CI, 1.08-1.94; P=0.01). Also we found an association of the CD28 IVS3 +17T/C variant with kidney allograft rejection cases (CC +CT/TT OR, 1.72; 95% CI, 1.19-2.49; P=0.004) and (C allele OR, 1.74; 95% CI, 1.11-2.75; P=0.02), but not established for liver allograft rejection cases (CC +CT/TT OR, 1.19; 95% CI, 0.47-2.98; P=0.72) and (C allele OR, 0.96; 95% CI, 0.67-1.39; P=0.84). And we found an association of the CD86 +1057G/A variant with non-allograft rejection cases (AA +AG/GG OR, 0.35; 95% CI, 0.14-0.85; P=0.02). This meta-analysis demonstrates that the CD28 IVS3 +17T/C variant might increase acute allograft rejection risk in kidney transplant but not in liver transplant, and there was an association between CD86 +1057G/A variant and reduced acute rejection risk. Further studies will be needed to confirm our findings.

Effects of the NQO1 609C>T Polymorphism on Leukemia Susceptibility: Evidence from a Meta-analysis

A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta- analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR = 1.23, 95%CI = 1.00 - 1.51, heterogeneity = 0.76; I2 = 0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed.

Curcumin inhibits human cytomegalovirus by downregulating heat shock protein 90

Curcumin is a traditional Chinese medicine extracted from the rhizome of the herb Curcuma longa, which exhibits anti-human cytomegalovirus (HCMV) activity, however, the underlying mechanism remains to be elucidated. The present study reported that the pharmacogenomics of curcumin are similar to that of the antiviral drug, geldanamycin, which targets heat shock protein 90 (Hsp90). Comparative analysis of 3,000 clinical drugs demonstrated that curcumin had a positive association with the gene expression profiles of several drugs, among which the pharmacogenomics of the antiviral drug, geldanamycin, were most similar to that of curcumin. Molecular docking simulation analysis revealed that curcumin fit well in the binding pocket of Hsp90, with hydrogen bonds, hydrophobic interactions and conjugation to maintain adhesion. Consistently, HCMV infection of human embryonic lung fibroblast cells resulted in increased expression of Hsp90α, which was significantly inhibited by treatment with curcumin. These findings suggested that targeting Hsp90 contributed to the anti‑HCMV activity of curcumin.

Human cytomegalovirus infection and vascular disease risk: A meta-analysis.

BACKGROUND Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease. Numbers studies were conducted to analyze the association between HCMV infection and risk of vascular disease, but no clear consensus had been reached. The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. METHODS We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: (1) evaluating the association between HCMV infection and vascular disease; (2) case-control studies or nested case-control studies; (3) and supply the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. Ultimately, We included data from 68 studies, which altogether enrolled 12027 cases and 15386 controls from 24 countries. RESULTS HCMV IgG was detected 7376 in 10611 cases, HCMV IgM was detected 153 in 1486 cases and HCMV DNA was detected 654 in 2139 cases. Overall, people exposed to HCMV infection had higher risk than those not exposed for vascular disease (OR 1.70 [95% CI 1.43-2.03] IgG-based HCMV tests, 2.88 [95% CI 1.87-4.43] IgM-based HCMV tests and 2.56 [95% CI 1.46-4.49 PCR-based HCMV tests]). HCMV infection was clearly identified as a risk factor for vascular disease in Asian group, Caucasian group and other group, especially Asian group(OR 1.86 [95% CI 1.33-2.60] IgG-based HCMV tests, 3.57 [95% CI 1.94-6.60] IgM-based HCMV tests and 4.09 [95% CI 3.10-5.40 PCR-based HCMV tests]). CONCLUSION This meta-analysis suggested that HCMV infection is associated with an increased risk for vascular disease.

Cytomegalovirus infection and atherosclerosis risk: A meta‐analysis

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta‐analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta‐analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non‐atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG‐based HCMV tests, IgM‐based tests, PCR‐based tests, and pp65‐based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09‐4.51), 8.92(95%CI 3.17‐25.11), 6.75 (95%CI 3.50‐13.02), and 5.72(95%CI 1.51‐21.58), respectively. The meta‐analysis results showed that HCMV infection is significant connected with an increased risk for AS.

TNF-α and LT-α polymorphisms and the risk of leukemia: a meta-analysis.

Aim The aim of this study is to investigate whether TNF-α or LT-α polymorphisms are associated with the risk of leukemia. Methods A meta-analysis was performed to examine the association between the TNF-α −308 G>A and LT-α +252 A>G polymorphisms and the incidence of leukemia. We also performed subgroup analyses based on the classification of leukemias. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association. Results A total of 19 publications comprising 1,509 cases and 4,075 controls were selected in the study. An association between the risk of leukemia and the LT-α +252 AA genotype was found (GG + AG vs. AA, OR = 0.485, 95% CI 0.368-0.639, p = 0.000). After multivariable analysis TNF-α polymorphism showed no consistent association with leukemia. Conclusions This meta-analysis suggests that the LT-α +252 AA polymorphism is associated with the risk of leukemia.

Akebia saponin D alleviates hepatic steatosis through BNip3 induced mitophagy

Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD.