Association between Tumor Necrosis Factor-α 308G/A Gene Polymorphism and Silicosis Susceptibility: A Meta-Analysis

Background

Tumor necrosis factor-α (TNF-α) 308 G/A gene polymorphism has been reported to be associated with susceptibility to silicosis. However, the relevant study results are still inconsistent.

Objective and Methods

A meta-analysis was performed in order to drive a more precise estimation of the relationship between TNF-α-308 G/A gene polymorphism and susceptibility to silicosis. Electronic databases were searched and nine separate studies were included. The pooled odds ratios (ORs) and the corresponding 95% confidence internal (CI) were calculated by a fixed effect model.

Results

A total of 1267 cases and 1214 controls were included. In the overall analysis, significantly increased silicosis risk was found (for GA+AA vs. GG OR=1.45, 95%CI: 1.20-1.760, P=1.58E4; for GA vs. GG: OR=1.53, 95%CI=1.25-1.86, P=3.11E5; for A allele vs. G allele: OR=1.27, 95%CI=1.08-1.50, P= 0.004). In the subgroup analysis, significantly increased silicosis risk was also found among Asians (for GA+AA vs. GG: OR=1.63, 95%CI=1.27-2.08, P=1.01E4), for GA vs. GG: OR=1.71, 95%CI=1.33-2.20, P=3.44E5), for A allele vs. G allele: OR=1.45, 95%CI=1.17-1.80, P=0.001). However, no significantly increased risk was found among non-Asians for all genetic models.

Conclusions

TNF-α-308 G/A polymorphism might lead to an increased risk of silicosis susceptibility, especially for Asians. However, further studies with large sample sizes should be conducted to confirm the association.     

Association of Human Leukocyte Antigen Class II with Susceptibility to Primary Biliary Cirrhosis: A Systematic Review and Meta-Analysis

Purpose

Several previous studies suggested that HLA-Class II may be associated with susceptibility to primary biliary cirrhosis (PBC), but data from individual studies remain controversial. Therefore, a systematic review and meta-analysis is needed to comprehensively evaluate the association between HLA-Class II and PBC risk.

Methods

All published reports of an association between HLA class II and PBC risk were searched in PubMed, EMBASE (updated to 22 May 2012). ORs with 95% confidence intervals (CIs) were extracted from each included study and the meta-analysis was performed using the fixed- or random-effects model.

Results

A total of 3,732 PBC patients and 11,031 controls from 34 studies were included in the meta-analysis. An assessment of study quality revealed that the majority of studies included (18 studies) were of high quality. The serological group DR8 was found to be a risk factor for PBC (OR = 2.82, 95%CI: 1.84–4.30). At the allelic level, HLA-DR*08 and HLA-DR*0801 were identified as risk factors for PBC (OR = 2.30, 95%CI: 1.76-3.00; OR = 3.23, 95%CI: 2.22–4.70, respectively), whereas HLA-DR*11 and HLA-DR*13 were potent protective factors (OR = 0.31, 95%CI: 0.27-0.38; OR = 0.62, 95%CI: 0.48-0.81, respectively). HLA-DQB1 and HLA-DQB1*0402 conferred a predisposition to PBC development (OR = 3.47, 95%CI: 2.35–5.13), whereas HLA-DQB1*0604 was protective against PBC (OR = 0.3, 95%CI: 0.18–0.58). No HLA-DPB1 allele was observed to be associated with PBC susceptibility (P > 0.05).

Conclusions

The present study revealed that HLA-Class II components are closely associated with the development of PBC.     

Association of VEGF Gene Polymorphisms with Diabetic Retinopathy: A Meta-Analysis

Background

Studies on the association of vascular endothelial growth factor (VEGF) gene -460T/C and -2578C/A polymorphisms with diabetic retinopathy (DR) have reported conflicting results. The aim of the present study was to assess the association by using meta-analysis.

Methods

A systematic search of electronic databases (PubMed, EMBASE, Elsevier Science Direct, ISI Web of Science, CBM, CNKI and VIP) was carried out until Sept 18, 2013. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.

Results

Eleven studies (-460T/C: 6 studies including 932 cases and 722 controls; -2578C/A: 6 studies including 1,071 cases and 1,137 controls) were involved in this meta-analysis. Significant association was found for -460T/C polymorphism (C versus T: OR=1.48, 95%CI=1.07–2.05, P=0.02; TC+CC versus TT: OR=1.78, 95%CI=1.02–3.12, P=0.04; CC versus TT+TC: OR=1.76, 95%CI=1.10–2.81, P=0.02), but not for -2578C/A polymorphism (P>0.05). Similar results were found in the subgroup analysis.

Conclusions

This meta-analysis demonstrates that DR is associated with VEGF gene -460T/C polymorphism, but not -2578C/A polymorphism. Further case-control studies based on larger sample size are still needed, especially for -2578C/A polymorphism.     

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

Background

Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.

Methods

A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina^® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).

Results

Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (P_combined = 1.54x10^-5; odds ratio (OR) = 7.27; 95% CI = 2.96–17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (P_combined = 1.29x10^-3; OR = 4.21; 95% CI = 1.75–10.11) overlapping MICA/HCP5/HCG26 genes.

Conclusion

Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.     

Association of HDL-Related Loci with Age-Related Macular Degeneration and Plasma Lutein and Zeaxanthin: the Alienor Study

Background

Several genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations.

Methods

Alienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1).

Results

After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance.

Conclusion

These findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.     

The Role of Prostatitis in Prostate Cancer: Meta-Analysis

Objective

Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model.

Evidence Acquisition

Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. Selection criteria: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases.

Evidence Synthesis

In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62), and random effects model (OR=1.64, 95%CI: 1.36-1.98). Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29), compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45). Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990’s: OR=1.58, 95% CI: 1.35-1.84; 2000’s: OR=1.59, 95% CI: 1.40-1.79; 2010’s: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990’s: OR=1.98, 95% CI: 1.08-3.62; 2000’s: OR=1.64, 95% CI: 1.23-2.19; 2010’s: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90.CONCLUSIONS: the present meta-analysis provides the statistical evidence that the association between prostatitis and prostate cancer is significant.     

Sex Differences in the Relationship between Asthma and Overweight in Dutch Children: a Survey Study

Objective

Obesity has been identified as a risk factor for asthma in children. However, in the Netherlands, the obesity prevalence is rising while the asthma prevalence in children is stabilising. The aim of this study is to clarify the association between asthma and Body Mass Index (BMI) in children and whether this association is influenced by sex.

Study Design

Parents of 39,316 children (6-16 years) in the south of the Netherlands were invited to complete an online questionnaire on respiratory symptoms, anthropometric variables and several potential confounding factors for asthma and obesity (including sex, birth weight and breastfeeding). Data was analysed by multivariable logistic regression models and an ordinal regression model.

Results

The response rate was 24% (n boys= 4,743, n girls= 4,529). The prevalence of asthma, overweight and obesity was 8%, 15% and 2% respectively. Body mass index - standard deviation Score (BMI-SDS) was related to current asthma (adjusted OR: 1.29; 95%CI: 1.14-1.45, p≤0.001). When stratified for sex, asthma and BMI-SDS were only related in girls (Girls: adjusted OR: 1.31; 95%CI: 1.13-1.51, p≤0.001. Boys: adjusted OR: 1.01; 95%CI: 0.91-1.14, p=0.72).

Conclusions

The positive association between BMI-SDS and asthma is only present in girls, not boys. Future studies into obesity and asthma should correct for sex in their analyses.     

Higher Carbohydrate Antigen 125 Levels Are Associated with Increased Risk of Coronary Heart Disease in Elderly Chinese: A Population-Based Case-Control Study

Background

High carbohydrate antigen 125 (CA-125) level was reported to be associated with some cardiac dysfunctions, such as chronic heart failure, but the relationship between CA-125 level and coronary heart disease (CHD) risk remains unclear. The aim of this study was to explore the potential association in a Chinese older population.

Methods

In a population-based case-control study conducted in a Chinese older population, serum CA-125 levels were measured in 1177 diagnosed CHD patients and 3531 age and sex matched control subjects without CHD.

Results

Serum CA-125 level was significantly higher in CHD patients than controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI, physical activity, hypertension, dyslipidemia, diabetes mellitus, medication history and family history of CHD and myocardial infarction. CHD risk was doubled (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to those in the lowest quartile of CA-125 level (P _trend < 0.001). Furthermore, CA-125 levels were associated with CHD risks in subjects with age over 60 years (OR: 2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04, 95%CI: 1.71-2.43).

Conclusions

Elevated serum CA-125 level might be associated with increased risk of coronary heart disease in the Chinese older population. Further investigations are needed to identify the possible biological role of CA-125 in CHD development in the future.     

Trans-Ethnical Shift of the Risk Genotype in the CETP I405V with Longevity: A Chinese Case-Control Study and Meta-Analysis

Background

The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity.

Methods

We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification.

Results

Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P _additive=0.008; P _dominant=0.008, OR_dominant=0.673; P _recessive=0.017, OR_recessive=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans.

Conclusion

Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.     

Association of Six Well-Characterized Polymorphisms in TNF-α and TNF-β Genes with Sarcoidosis: A Meta-Analysis

Backgrounds

In this study, we aimed to investigate the association of six well-characterized polymorphisms in tumor necrosis factor alpha and beta (TNF-α and TNF-β) genes with the risk for sarcoidosis via a comprehensive meta-analysis.

Methods And Findings

The electronic MEDLINE (Ovid) and PubMed databases covering the period from the earliest possible year to June 2013 were searched. Total 13 qualified articles including 1584 patients with sarcoidosis and 2636 controls were recruited. The data were analyzed by RevMan software, and risk estimates were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses of the full data set failed to identify any significant association of TNF-α gene -307A (OR=1.25; 95% CI: 0.98-1.59), -1031C (OR=0.88; 95% CI: 0.71-1.1), -863A (OR=0.89; 95% CI: 0.72-1.11), -238A (OR=0.97; 95% CI: 0.71-1.32), and -857T (OR=1.14; 95% CI: 0.74-1.77) alleles, but a significant association for TNF-β 252A allele (OR=1.65; 95%CI = 1.33-2.04; P<0.00001). Under a random-effects allelic model, there was marginally significant increased risk of sarcoidosis for -307A allele among Caucasians (OR=1.25; 95% CI: 0.96-1.62; P=0.09) but not among Asians (OR=2.12; 95% CI: 0.31-14.27; P=0.44). There was a low probability of publication bias as reflected by the fail-safe number.

Conclusions

This meta-analysis extended previous findings on the association between the TNF-α and TNF-β genetic polymorphisms and sarcoidosis, by showing that the TNF-β gene A252G polymorphism might be a potential risk factor for the development of sarcoidosis.     

Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome

Purpose

To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS).

Methods

This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05)in PATIENTS.

Results

BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26–3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15–9.40, p<0.001).

Conclusions

After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.     

Association between Mannose-Binding Lectin Gene Polymorphisms and Hepatitis B Virus Infection: A Meta-Analysis

Objective

The results of studies on the relation between Mannose-binding lectin gene (mbl2) polymorphism and HBV infection were contradictory and inconclusive. In order to shed a light on these inconsistent findings and to clarify the role of mbl2 polymorphisms in susceptibility or progression of chronic hepatitis B (CHB), a meta-analysis was performed.

Methods

PubMed and Embase were searched for available articles. A meta-analysis was performed to examine the association between mbl2 polymorphisms and chronicity or progression of hepatitis B infection. Odds ratio (OR) and its 95% confidence interval (CI) served as indexes.

Results

A total of 17 eligible studies were involved, including 2151 healthy controls (HC), 1293 spontaneous recovered (SR) patients with acute infection, 2337cases with chronic hepatitis B (CHB) and 554 cases with progressive hepatitis B. There was no evidence of significant association between mbl2 exon1 polymorphisms and CHB risk in any genetic model or pairwise comparisons when compared with HC group or SR group. In the stratified analysis of ethnic groups, also no obvious relation between mbl2 polymorphism and CHB risk was identified. There was still no significant association between the complete mbl2 genotypic profile (including both the exon1 and the promoter gene) polymorphisms and CHB risk, as compared with SR group. However, it was found that there was an association between the mbl2 AO/OO genotype and severe hepatitis B (SHB) or liver cirrhosis (LC) (LC vs. HC:OR=3.66, 95%CI, 2.38-5.63; SHB vs. HC, OR=3.88, 95%CI, 2.26–6.64), but there was no relationship between the mbl2 AO/OO genotype and hepatocellular carcinoma (HCC) (OR=1.26, 95%CI, 0.82-1.94).

Conclusion

The present meta-analysis indicated that mbl2 exon1 polymorphisms might not significantly associate with chronicity of HBV infection, but might be significantly related to the progressive HBV such as SHB and LC.     

NT-proBNP Best Predictor of Cardiovascular Events and Cardiovascular Mortality in Secondary Prevention in Very Old Age: The Leiden 85-Plus Study

Background

In the aging population cardiovascular disease (CVD) is highly prevalent. Identification of very old persons at high risk of recurrent CVD is difficult, since traditional risk markers loose predictive value with age.

Methods

In a population-based sample of 282 85-year old participants with established CVD from the Leiden 85-plus Study, we studied predictive values of traditional cardiovascular risk markers, a history of major CVD (myocardial infarction, stroke or arterial surgery), and new cardiovascular biomarkers (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP), homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding 5-year risk of recurrent cardiovascular events and mortality (composite endpoint).

Results

During complete 5-year follow-up 157 (56%) participants died. 109 (39%) had a cardiovascular event or died from cardiovascular causes. Individually related to the composite endpoint were: a history of major CVD (HR 1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI 1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of all five new markers only addition of NT-proBNP improved the C-statistic (0.67 (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and for homocysteine 24.7% (p=0.04).

Conclusions

Among very old subjects with established CVD, NT-proBNP was the strongest risk marker for cardiovascular events and cardiovascular mortality. When estimating risk in secondary prevention in very old age, use of NT-proBNP should be considered.     

FTO Gene Variant and Risk of Overweight and Obesity among Children and Adolescents: a Systematic Review and Meta-Analysis

Objective

The fat mass and obesity associated gene (FTO) polymorphisms have been implicated in the susceptibility of overweight/obesity in children and adolescents. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of FTO gene polymorphisms with overweight/obesity risk among children and adolescents.

Methods

PubMed and Embase were used to search for eligible published literatures. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models.

Results

A total of 21 articles containing 23 studies (11208cases and 35015controls) were included in our analysis. The results indicated that variant in FTO gene was significantly associated with increased risk of overweight/obesity in children and adolescents (OR=1.35; 95%CI: 1.27-1.44; P<0.001). The overall pooled ORs for risk obesity and overweight were 1.34 (95%CI: 1.21-1.48) and 1.35 (95%CI: 1.25-1.47), respectively. Subgroup analyses also showed similar trends in most subgroups of adjustment for covariates and unadjustment, different ethnicities (Caucasians, Asians, and Amerindians), and each of three investigated polymorphisms (rs9939609, rs1421085, and rs1558902).

Conclusions

The present meta-analysis suggested a positive association between FTO gene polymorphism and overweight/obesity risk among children and adolescents. Further prospective studies should be recommended to confirm the observed association, and underlying mechanism should be investigated to clarify the association of FTO gene polymorphism with overweight/obesity.     

Tuberculosis in Healthcare Workers and Infection Control Measures at Primary Healthcare Facilities in South Africa

Background

Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers.

Methods

One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained.

Results

The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08).

Conclusion

The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.     

High Postoperative Serum Cortisol Level Is Associated with Increased Risk of Cognitive Dysfunction Early after Coronary Artery Bypass Graft Surgery: A Prospective Cohort Study

Context

Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction.

Objective

To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery.

Design

Prospective cohort study.

Setting

Two teaching hospitals.

Patients

One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009.

Intervention

None.

Main Outcome Measures

Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction.

Results

Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016).

Conclusions

High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.     

Influence of the CXCL1 rs4074 A Allele on Alcohol Induced Cirrhosis and HCC in Patients of European Descent

Background and Aims

CXCL1 (CXC chemokine-ligand-1) is a ligand for CXC chemokine receptor 2 expressed on hepatic stellate cells (HSC). Thus, CXCL1 might contribute to HSC activation and fibrogenesis. In the present study, we investigated the influence of the CXCL1 rs4074 polymorphism on the occurrence of alcohol induced liver cirrhosis and hepatocellular carcinoma (HCC).

Methods

The study involved 458 patients with alcoholic cirrhosis (170 with HCC), 115 alcoholics without liver disease and 342 healthy controls. All subjects were genotyped for the CXCL1 rs4074 polymorphism and CXCL1 serum levels of 132 patients were measured. In vitro CXCL1 secretion in TLR-transfected cell lines were studied by ELISA.

Results

Distribution of the CXCL1 genotypes (GG/GA/AA) was 159/219/80 in patients with alcoholic cirrhosis, 52/44/19 in alcoholic controls and 158/140/44 in healthy controls. Patients with alcohol-induced cirrhosis were significantly more often carriers of the CXCL1 rs4074 A allele (65.3%) than alcoholics without liver disease (54.8%, OR=1.55; 95%CI=1.025-2.350; p=0.04) and healthy controls (53.8%, OR=1.62; 95%CI=1.212-2.151; p=0.001). Accordingly, the frequency of the CXCL1 rs4074 A allele was significantly higher in the cirrhotic patients than in the subjects without cirrhosis (41.4% vs. 33.9%, OR=1.38, 95% CI:1.14–1.66, p=0.001). Furthermore cirrhotic carriers of the CXCL1 rs4074 A allele had significantly higher CXCL1 serum levels than carriers of the GG genotype. In contrast to sera from healthy controls, sera from patients with alcoholic cirrhosis induced CXCL1 secretion in TLR2- (p=0.016) and TLR4- (p=0.008) transfected HEK293 cells. This finding indicates that sera from patients with alcoholic cirrhosis contain soluble ligands that can induce CXCL1 production via stimulation of TLRs.

Conclusion

The enhanced CXCL1 serum levels in carriers of the rs4074 A allele together with their increased frequency in patients with alcohol induced cirrhosis suggest the CXCL1 rs4074 A allele as a genetic risk factor for alcoholic cirrhosis.     

Prevalence and Associated Factors for Pterygium in Rural Agrarian Central India. The Central India Eye and Medical Study

Purpose

To evaluate the prevalence of pterygia and associated factors in a rural population in a mostly undeveloped agrarian region.

Methods

The Central India Eye and Medical Study is a population-based study performed in a rural region of Central India. The study comprised 4711 subjects (aged 30+ years). A detailed ophthalmic and medical examination was performed. A pterygium was diagnosed during the slit lamp examination and confirmed on corneal photographs. It was defined as a fleshy fibrovascular growth, crossing the limbus and typically seen on the nasal, and sometimes temporal, conjunctiva.

Results

A pterygium was detected in 798 eyes (prevalence rate: 8.47±0.29%) of 608 (12.91±0.49%) subjects. Bilateral pterygia were present in 190 subjects (4.0% of study population). Pterygia prevalence increased from 6.7±0.8% in the age group 30-39 years, to 13.5±1.2% in the age group 50-59 years, to 25.3±2.1% in the age group 70-79 years. Prevalence of pterygia was associated with older age (P<0.001; regression coefficient B: 0.02; odds ratio (OR): 1.02; 95%CI: 1.01, 1.03), male gender (P<0.001;B:-0.73;OR: .48;95%CI:0.39,0.61), lower level of education (P<0.001;B:-0.30;OR:0.74;95%CI:0.69,0.80), lower body height (P=0.001;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.26;95%CI:1.18,1.34). If the education level was dropped, the number of hours spent with vigorous activity outdoors (P=0.001;B:0.001;OR:1.001;95%CI:1.000,1.0001) was significantly associated with the prevalence of pterygia, in addition to older age (P<0.001;B:0.03;OR:1.03;95%CI:1.03,1.04), male gender (P<0.001;B:-0.49;OR:0.62;95%CI:0.49,0.77), lower body height (P=0.005;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.25;95%CI:1.18,1.34).

Conclusions

Pterygium prevalence in rural Central India is about 13% among adult Indians aged 30+ years. Older age, male gender, lower educational level, lower body height and more time spent outdoors with vigorous work were associated factors. Since the living conditions in the study location were mostly untouched by modern developments, the results may show the prevalence and associations of pterygia without major medical or technologic influences.     

Association Analysis of Genetic Variants in the Myosin IXB Gene in Acute Pancreatitis

Introduction

Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis.

Methods

Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls.

Results

Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology.

Conclusion

Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2.     

Associations between Tumor Necrosis Factor-α Polymorphisms and Risk of Psoriasis: A Meta-Analysis

Background

Tumor necrosis factor-α (TNF-α) may play an important role in the recalcitrant inflammatory and hyperproliferative dermatosis of psoriasis, and there may be a relationship between TNF-α polymorphisms and psoriasis risk.

Methods

We performed a meta-analysis to evaluate the associations between TNF-α polymorphisms and psoriasis. Electronic searches of Pubmed, Embase, and Web of Science were performed for all publications on the associations between TNF-α polymorphisms and psoriasis through September 26, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the associations.

Results

Sixteen case-control studies with a total of 2,253 psoriasis cases and 1,947 controls on TNF-α 308 G/A polymorphism and fourteen studies on TNF-α 238 G/A polymorphism with 2,104 cases and 1,838 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with decreased risk of psoriasis under three genetic comparison models (for A versus G: fixed-effects OR 0.71, 95%CI 0.62-0.82, P < 0.001; for AG versus GG: fixed-effects OR 0.67, 95%CI 0.57-0.78, P < 0.001; for AA/AG versus GG: fixed-effects OR 0.67, 95%CI 0.58-0.78, P < 0.001). In addition, TNF-α 238 G/A polymorphism was associated with increased risk of psoriasis under three genetic models (for A versus G: fixed-effects OR 2.46, 95%CI 2.04-2.96, P < 0.001; for AG versus GG: fixed-effects OR 2.69, 95%CI 2.20-3.28, P < 0.001; for AA/AG versus GG: fixed-effects OR 2.68, 95%CI 2.20-3.26, P < 0.001). Subgroup analysis by ethnicity identified a significant association between TNF-α 308 G/A polymorphism and decreased risk of psoriasis in both Caucasians and Asians and a significant association between TNF-α 238 G/A polymorphism and increased risk of psoriasis in Caucasians.

Conclusions

The meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with decreased risk of psoriasis, while TNF-α 238 G/A is associated with increased risk of psoriasis.