The -2518A/G Polymorphism in the MCP-1 Gene and Tuberculosis Risk: A Meta-Analysis

Background

The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene has been implicated in the susceptibility to tuberculosis (TB), but the results are not conclusive. The aim of this study is to investigate the association between the -2518A/G polymorphism in the MCP-1 gene and the risk of tuberculosis by meta-analysis.

Methods

We searched Pubmed, Embase, CNKI and Wanfang databases, covering all studies until April 29^th, 2011. Statistical analyses were performed using the Revman4.2 and STATA10.0 software.

Results

A total of 5341 cases and 6075 controls in 13 case-control studies were included in the meta-analysis. The results indicated that the GG homozygote carriers had a 67% increased risk of TB compared with the A allele carriers (GG vs. GA+AA: OR = 1.67, 95%CI = 1.25–2.23, P = 0.0006). In the subgroup analysis by ethnicity, significant elevated risks were found in Asians and Latinos, but not in Africans (GG vs. GA+AA: OR = 1.79, 95%CI = 1.19–2.70 and P = 0.005 for Asians; OR = 2.15, 95%CI = 1.32–3.51 and P = 0.002 for Latinos; OR = 1.28, 95%CI = 0.45–3.64 and P = 0.65 for Africans).

Conclusion

This meta-analysis suggested that the -2518A/G polymorphism of MCP-1 gene would be a risk factor for TB in Asians and Latinos, while not in Africans.     

The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis

Background

A number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model.

Results

Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008).

Conclusions

This meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.     

Renal function and risk factors of moderate to severe chronic kidney disease in Golestan Province, northeast of Iran

Introduction

The incidence of end-stage renal disease is increasing worldwide. Earlier studies reported high prevalence rates of obesity and hypertension, two major risk factors of chronic kidney disease (CKD), in Golestan Province, Iran. We aimed to investigate prevalence of moderate to severe CKD and its risk factors in the region.

Methods

Questionnaire data and blood samples were collected from 3591 participants (≥18 years old) from the general population. Based on serum creatinine levels, glomerular filtration rate (GFR) was estimated.

Results

High body mass index (BMI) was common: 35.0% of participants were overweight (BMI 25–29.9) and 24.5% were obese (BMI ≥30). Prevalence of CKD stages 3 to 5 (CKD–S3-5), i.e., GFR <60 mL/min/1.73 m², was 4.6%. The odds ratio (OR) and 95% confidence interval (95% CI) for the risk of CKD–S3-5 associated with every year increase in age was 1.13 (1.11–1.15). Men were at lower risk of CKD–S3-5 than women (OR = 0.28; 95% CI 0.18–0.45). Obesity (OR = 1.78; 95% CI 1.04–3.05) and self-reported diabetes (OR = 1.70; 95% CI 1.00–2.86), hypertension (OR = 3.16; 95% CI 2.02–4.95), ischemic heart disease (OR = 2.73; 95% CI 1.55–4.81), and myocardial infarction (OR = 2.69; 95% CI 1.14–6.32) were associated with increased risk of CKD–S3-5 in the models adjusted for age and sex. The association persisted for self-reported hypertension even after adjustments for BMI and history of diabetes (OR = 2.85; 95% CI 1.77–4.59).

Conclusion

A considerable proportion of inhabitants in Golestan have CKD–S3-5. Screening of individuals with major risk factors of CKD, in order to early detection and treatment of impaired renal function, may be plausible. Further studies on optimal risk prediction of future end-stage renal disease and effectiveness of any screening program are warranted.     

Pandemic Influenza (A/H1N1) Vaccine Uptake among French Private General Practitioners: A Cross Sectional Study in 2010

Background

In July, 2009, French health authorities, like those in many other countries, decided to embark on a mass vaccination campaign against the pandemic A(H1N1) influenza. Private general practitioners (GPs) were not involved in this campaign. We studied GPs’ pandemic vaccine (pvaccine) uptake, quantified the relative contribution of its potential explanatory factors and studied whether their own vaccination choice was correlated with their recommendations to patients about pvaccination.

Methodology/Principal Findings

In this cross-sectional telephone survey, professional investigators interviewed an existing panel of randomly selected private GPs (N = 1431; response rate at inclusion in the panel: 36.8%; participation rate in the survey: 100%). The main outcome variable was GPs’ own pvaccine uptake. We used an averaging multi-model approach to quantify the relative contribution of factors associated with their vaccination. The pvaccine uptake rate was 61% (95%CI = 58.3–63.3). Four independent factors contributed the most to this rate (partial Nagelkerke’s R²): history of previous vaccination against seasonal influenza (14.5%), perception of risks and efficacy of the pvaccine (10.8%), opinions regarding the organization of the vaccination campaign (7.1%), and perception of the pandemic''s severity (5.2%). Overall, 71.3% (95%CI = 69.0–73.6) of the participants recommended pvaccination to young adults at risk and 40.1% (95%CI = 37.6–42.7) to other young adults. GPs’ own pvaccination was strongly predictive of their recommendation to both young adults at risk (OR = 9.6; 95%CI = 7.2–12.6) and those not at risk (OR = 8.5; 95%CI = 6.4–11.4).

Conclusions/Significance

These results suggest that around 60% of French private GPs followed French authorities’ recommendations about vaccination of health care professionals against the A(H1N1) influenza. They pinpoint priority levers for improving preparedness for future influenza pandemics. Besides encouraging GPs'' own uptake of regular vaccination against seasonal influenza, providing GPs with clear information about the risks and efficacy of any new pvaccine and involving them in the organization of any future vaccine campaign may improve their pvaccine uptake.     

Association between CD209 -336A/G and -871A/G Polymorphisms and Susceptibility of Tuberculosis: A Meta-Analysis

Background

The association between CD209 promoter polymorphisms (-336A/G, -871A/G) and tuberculosis (TB) risk has been widely reported, but results of previous studies remain controversial and ambiguous. To assess the association between CD209 polymorphisms and TB risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, we identified outcome data from all articles estimating the association between CD209 polymorphisms and TB risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 14 studies with 3,610 cases and 3,539 controls were identified. There was no significant association between CD209 -336A/G polymorphism and TB risk (OR = 1.04, 95% CI = 0.91–1.19 for G vs. A; OR = 1.13, 95% CI = 0.84–1.53 for GG vs. AA; OR = 1.04, 95% CI = 0.87–1.24 for GG+AG vs. AA; OR = 1.11, 95% CI = 0.88–1.39 for GG vs. AG+AA). However, the significant association was revealed for Asians in GG vs. AA (OR = 2.48, 95% CI = 1.46–4.22, P = 0.0008) and GG vs. AG+AA (OR = 2.10, 95% CI = 1.33–3.32, P = 0.001). For the CD209 -871A/G polymorphism, lack of an association was also found (OR = 0.81, 95% CI = 0.70–0.95 for G vs. A; OR = 1.00, 95% CI = 0.52–1.93 for GG vs. AA; OR = 0.73, 95% CI = 0.60–0.89 for GG+AG vs. AA; OR = 1.09, 95% CI = 0.57–2.10 for GG vs. AG+AA).

Conclusion

The present meta-analysis suggested that CD209 promoter polymorphisms (-336A/G, -871A/G) were unlikely to substantially contribute to TB susceptibility. However, the GG genotype of CD209 -336A/G polymorphism might be a genetic risk factor that increases TB susceptibility for Asians in GG vs. AA and GG vs. AG+AA.     

Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and Colorectal Cancer Risk

Background

Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.

Methods

Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.

Results

This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83–0.98; dominant model, OR = 0.92, 95%CI = 0.85–0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy–Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies’ publication time, the results were persistent and robust.

Conclusion

This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.     

Association study of the β2-adrenergic receptor gene polymorphisms and hypertension in the Northern Han Chinese

Background

The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population.

Methodology/Principal Findings

This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk.

Conclusions/Significances

We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.     

Association between Single Nucleotide Polymorphisms in ERCC4 and Risk of Squamous Cell Carcinoma of the Head and Neck

Background

Excision repair cross-complementation group 4 gene (ERCC4/XPF) plays an important role in nucleotide excision repair and participates in removal of DNA interstrand cross-links and DNA double-strand breaks. Single nucleotide polymorphisms (SNPs) in ERCC4 may impact repair capacity and affect cancer susceptibility.

Methodology/Principal Findings

In this case-control study, we evaluated associations of four selected potentially functional SNPs in ERCC4 with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,040 non-Hispanic white patients with SCCHN and 1,046 cancer-free matched controls. We found that the variant GG genotype of rs2276466 was significantly associated with a decreased risk of SCCHN (OR = 0.69, 95% CI 0.50–0.96), and that the variant TT genotype of rs3136038 showed a borderline significant decreased risk with SCCHN (OR = 0.76, 95% CI: 0.58–1.01) in the recessive model. Such protective effects were more evident in oropharyngeal cancer (OR = 0.61, 95% CI: 0.40–0.92 for rs2276466; OR = 0.69, 95% CI: 0.48–0.98 for rs3136038). No significant associations were found for the other two SNPs (rs1800067 and rs1799798). In addition, individuals with the rs2276466 GG or with the rs3136038 TT genotypes had higher levels of ERCC4 mRNA expression than those with the corresponding wild-type genotypes in 90 Epstein-Barr virus-transformed lymphoblastoid cell lines derived from Caucasians.

Conclusions

These results suggest that these two SNPs (rs2276466 and rs3136038) in ERCC4 may be functional and contribute to SCCHN susceptibility. However, our findings need to be replicated in further large epidemiological and functional studies.     

Associations between XPD Asp312Asn polymorphism and risk of head and neck cancer: a meta-analysis based on 7,122 subjects

Background

To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.

Methods

We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.

Results

Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P _{heterogeneity} = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P _{heterogeneity} = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P _{heterogeneity} = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P _{heterogeneity} = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.

Conclusions

This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.     

Bradykinin β(2) Receptor -58T/C Gene Polymorphism and Essential Hypertension: A Meta-Analysis

Background

Research has shown that bradykinin β₂ receptor (BDKRB2) −58T/C gene polymorphism is correlated with the risk of essential hypertension (EH), but the results remain inconclusive.

Objective and Methods

The objective of this study was to explore the association between BDKRB2−58T/C gene polymorphism and EH. A meta-analysis of 11 studies with 3882 subjects was conducted. Pooled odds ratios (ORs) for the association between BDKRB2−58T/C gene polymorphism and EH and their corresponding 95% confidence intervals (CIs) were estimated using the random effects model.

Results

The BDKRB2−58T/C gene polymorphism was significantly correlated with EH under an allelic genetic model (OR = 1.24, 95% CI = 1.05–1.46; P = 0.01), a dominant genetic model (OR = 0.65, 95% CI = 0.47–0.90; P = 0.01), a recessive genetic model (OR = 1.146, 95% CI = 1.035–1.269; P = 0.009), a homozygote genetic model (OR = 1.134, 95% CI = 1.048–1.228; P = 0.002), and a heterozygote genetic model (OR = 1.060, 95% CI = 1.009–1.112; P = 0.019).

Conclusions

The BDKRB2−58T/C gene polymorphism is associated with increased EH risk. The results of this study suggest that carriers of the −58C allele are susceptible to EH.     

Shortened telomere length is associated with increased risk of cancer: a meta-analysis

Background

Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting.

Methods

A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the χ²-based Q statistic test and Egger''s test, respectively.

Results

The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14–1.60), compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38–2.44), lung cancer (OR = 2.39, 95% CI = 1.18–4.88), smoking-related cancers (OR = 2.25, 95% CI = 1.83–2.78), cancers in the digestive system (OR = 1.69, 95% CI = 1.53–1.87) and the urogenital system (OR = 1.73, 95% CI = 1.12–2.67). Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger''s test suggested that there was no publication bias in the current meta-analysis (P = 0.532).

Conclusions

The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings.     

Association of caucasian-identified variants with colorectal cancer risk in singapore chinese

Background

Genome-wide association studies (GWAS) in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs) that influence colorectal cancer (CRC) risk.

Methods

We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs), in high linkage disequilibrium (LD, r²≥0.8) and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH) cases and controls.

Results

Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR) ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63–0.88) but not disease prognosis (OR = 0.91, 95% CI 0.69–1.20). Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14–1.58) but not women (OR = 1.07, 95% CI: 0.88–1.29), suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ∼1; p-value >0.1). Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies.

Conclusions

The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.     

Intake of Gnetum Africanum and Dacryodes Edulis, Imbalance of Oxidant/Antioxidant Status and Prevalence of Diabetic Retinopathy in Central Africans

Objective

To estimate the prevalence of DR and to correlate cardiometabolic, sociodemographic, and oxidant/antioxidant imbalance data to the prevalence of DR.

Design

This case-control study included type 2 DM (T2 DM) patients with DR (n = 66), T2 DM patients without DR (N = 84), and healthy controls (n = 45) without DR, in Kinshasa town. Diet, albuminemia, serum vitamins, and 8-isoprostane were examined.

Results

No intake of safou (OR = 2.7 95% CI 1.2–5.8; P = 0.014), low serum albumin <4.5 g/dL (OR-2.9 95% CI 1.4–5.9; P = 0.003), no intake of fumbwa (OR = 2.8 95% CI 1.2–6.5; P = 0.014), high 8-isoprostane (OR = 14.3 95% CI 4.5–46; P<0.0001), DM duration ≥5 years (OR = 3.8 95% CI 1.6–9.1; P = 0.003), and low serum vitamin C (OR = 4.5 95% CI 1.3–15.5; P = 0.016) were identified as the significant independent determinants of DR.

Conclusion

The important role of oxidant/antioxidant status imbalance and diet is demonstrated in DR.     

The association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies

Background

Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.

Methods

We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.

Results

The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98–1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13–1.48, and recessive model: OR = 1.19, 95% CI = 1.07–1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12–1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04–1.37, and recessive model OR = 1.23, 95% CI = 1.08–1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.

Conclusions

Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.     

Older men who use computers have lower risk of dementia

Objective

To determine if older men who use computers have lower risk of developing dementia.

Methods

Cohort study of 5506 community-dwelling men aged 69 to 87 years followed for up to 8.5 years. Use of computers measured as daily, weekly, less than weekly and never. Participants also reported their use of email, internet, word processors, games or other computer activities. The primary outcome was the incidence of ICD-10 diagnosis of dementia as recorded by the Western Australian Data Linkage System.

Results

1857/5506 (33.7%) men reported using computers and 347 (6.3%) received a diagnosis of dementia during an average follow up of 6.0 years (range: 6 months to 8.5 years). The hazard ratio (HR) of dementia was lower among computer users than non-users (HR = 0.62, 95%CI = 0.47–0.81, after adjustment for age, educational attainment, size of social network, and presence of depression or of significant clinical morbidity). The HR of dementia appeared to decrease with increasing frequency of computer use: 0.68 (95%CI = 0.41–1.13), 0.61 (95%CI = 0.39–0.94) and 0.59 (95%CI = 0.40–0.87) for less than weekly, at least weekly and daily. The HR of dementia was 0.66 (95%CI = 0.50–0.86) after the analysis was further adjusted for baseline cognitive function, as measured by the Mini-Mental State Examination.

Conclusion

Older men who use computers have lower risk of receiving a diagnosis of dementia up to 8.5 years later. Randomised trials are required to determine if the observed associations are causal.     

Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population

Background

Coal workers'' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.

Methods

We performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.

Results

The NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.07–1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR = 1.67, 95%CI = 1.15–2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.

Conclusions

This is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings.     

Association of microRNA-499 rs3746444 Polymorphism with Cancer Risk: Evidence from 7188 Cases and 8548 Controls

Background

Owing to inconsistent and inconclusive results, we performed a meta-analysis to derive a more precise estimation of the association between miR-499 rs3746444 polymorphism and cancer risk.

Methodology/Principal Findings

A systematic search of the Pubmed, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) databases was performed with the last search updated on May 6, 2012. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of the association. A total of 15 independent studies including 7,188 cases and 8,548 controls were used in the meta-analysis. In the present meta-analysis, we found a significant association between miR-499 rs3746444 polymorphism and cancer risk in the overall analysis (G versus A: OR = 1.10, 95%CI 1.01–1.19, P = 0.03; GG+AG versus AA: OR = 1.15, 95%CI 1.02–1.30, P = 0.02; GG versus AG+AA: OR = 1.07, 95%CI 0.89–1.28, P = 0.50; GG versus AA: OR = 1.13, 95%CI 0.98–1.31, P = 0.09; AG versus AA: OR = 1.16, 95%CI 1.02–1.33, P = 0.03). In the subgroup analysis by ethnicity, miR-499 rs3746444 polymorphism was significantly associated with cancer risk in Asian population. In the subgroup analysis by cancer types, miR-499 rs3746444 polymorphism was significantly associated with breast cancer.

Conclusions/Significance

This meta-analysis suggests a significant association between miR-499 rs3746444 polymorphism and cancer risk. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.     

Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies

Background

MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results.

Methodology/Principal Findings

We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR = 1.18, 95% CI = 1.03–1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR = 1.11, 95%CI = 1.01–1.23, P _{heterogeneity} = 0.210) and lung cancer risk (OR = 1.25, 95%CI = 1.06–1.46, P _{heterogeneity} = 0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR = 1.24, 95% CI = 1.07–1.43, P _{heterogeneity} = 0.006).

Conclusions

These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers.     

Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population

Background

To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women.

Methodology/Principal Findings

In this study, 1764 unrelated pregnant women were recruited, of which 725 women had GDM and 1039 served as controls. Six single nucleotide polymorphisms (rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK) were genotyped using TaqMan allelic discrimination assays. The genotype and allele distributions of each SNP between the GDM cases and controls and the combined effects of alleles for the risk of developing GDM were analyzed. We found that the rs4402960, rs2383208 and rs391300 were statistically associated with GDM (OR = 1.207, 95%CI = 1.029–1.417, p = 0.021; OR = 1.242, 95%CI = 1.077–1.432, p = 0.003; OR = 1.202, 95%CI = 1.020–1.416, P = 0.028, respectively). In addition, the effect was greater under a recessive model in rs391300 (OR = 1.820, 95%CI = 1.226–2.701, p = 0.003). Meanwhile, the joint effect of these three loci indicated an additive effect of multiple alleles on the risk of developing GDM with an OR of 1.196 per allele (p = 1.08×10⁻⁴). We also found that the risk alleles of rs2383208 (b = −0.085, p = 0.003), rs4402960 (b = −0.057, p = 0.046) and rs10830963 (b = −0.096, p = 0.001) were associated with HOMA-B, while rs7754840 was associated with decrease in insulin AUC during a 100 g OGTT given at the time of GDM diagnosis (b = −0.080, p = 0.007).

Conclusions/Significance

Several risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. The effects of these SNPs on GDM might be through the impairment of beta cell function and these risk loci contributed additively to the disease.     

Ethnicity and cutaneous melanoma in the city of Sao Paulo, Brazil: a case-control study

Background

Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil.

Methodology/Principal Findings

We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe—Spain (OR = 3.01, 95% CI: 1.03–8.77), Italy (OR = 3.47, 95% CI: 1.41–8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05–8.93), or ≥2 European countries (OR = 2.82, 95% CI: 1.06–7.47); eye color—light brown (OR = 1.99, 95% CI: 1.14–3.84) and green/blue (OR = 4.62; 95% CI 2.22–9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21–6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03–9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03–3.19).

Conclusions

Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.