Genetic Comparison Models Research Articles

Tumor Necrosis Factor-α 238 G/A Polymorphism and Risk of Hepatocellular Carcinoma: Evidence from a Meta-analysis

Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progression of cancer. Many epidemiological studies have evaluated associations between the TNF-α 238 G/A polymorphism and hepatocellular carcinoma (HCC) risk, but the published data are inconclusive. Therefore, we performed the present meta-analysis. Electronic searches of several databases were conducted for all publications on the association between TNF-α 238 G/A polymorphism and HCC through July 2012. Asummary odds ratio (OR) with its 95% confidence interval (CI) were calculated to evaluate the strength of this association. Eleven case-control studies with a total of 1,572 HCC cases and 1,875 controls were finally included in this meta-analysis. Overall, the TNF-α 238 G/A polymorphism was significantly associated with increased risk of hepatocellular carcinoma in three genetic comparison models (For A versus G: OR 1.32, 95%CI 1.04-1.69, P = 0.02, I2 = 40%; for AG versus GG: OR 1.32, 95%CI 1.02-1.71, P = 0.03, I2 = 40%; for AA/AG versus GG: OR 1.33, 95%CI 1.03-1.72, P = 0.03, I2 = 41%) when all studies were pooled. Subgroup analysis by ethnicity further showed that there was a significant association between the TNF-α 238 G/A polymorphism and risk of HCC in Asians under three genetic comparison models (For A versus G: OR 1.30, 95%CI 1.00-1.68, P = 0.05, I2 = 45% for AA/AG versus GG: OR 1.31, 95%CI 1.00-1.71, P = 0.05, I2 = 46%). This meta-analysis provided convincing evidence that the TNF-α 238 G/A polymorphism is associated with increased susceptibility to HCC. However, more well-designed studies with large sample size are needed to validate this association in Caucasians.

Angiotensin-converting enzyme insertion/deletion polymorphism and risk of myocardial infarction in an updated meta-analysis based on 34 993 participants

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism and risk of myocardial infarction (MI) has been extensively studied. However, the results were in controversy. This study aimed to explore the association between ACE I/D polymorphism and risk of MI by using a meta-analysis. We retrieved the following databases to indentify eligible studies: Medline, Embase, ISI, VIP, CBM and Wan Fang database. The latest update was 10th May, 2012. Odds ratio and 95% confidence interval (95% CI) were used to present the strength of the association. A total of 40 case–control studies with 34993 participants were included. Overall, D allele of ACE I/D polymorphism was significantly associated with an increased risk of MI in genetic comparison models (OR (95% CI): 1.41 (1.22–1.64) for DD vs. II; 1.11 (1.01–1.21) for ID vs. II; 1.23 (1.10–1.37) for D carriers vs. II; 1.28 (1.15–1.43) for DD vs. I carriers and 1.06 (1.02–1.10) for D carriers vs. I carriers). Subgroup analyses, according to ethnicities and countries of participants also indicated that D allele was significantly associated with an increased risk of MI in Asians (especially for Chinese) and Caucasians (especially for English, French, Germans and Italians) (OR (95% CI) of DD vs. ID+II: 2.11 (1.65–2.70) for Asians and 1.15 (1.05–1.27) for Caucasians). In conclusion, this meta-analysis indicated that D allele of ACE I/D polymorphism was a possible risk factor for MI incidence for both Asians and Caucasians.

A systemic assessment of the association between tumor necrosis factor alpha 308 G/A polymorphism and risk of cervical cancer

Tumor necrosis factor alpha (TNF-α) is a multifunctional cytokine which plays an important role in the human immune response against various pathogens, and there may be a relationship between TNF-α 308 G/A polymorphism and cervical cancer risk. We performed a meta-analysis to get a systemic assessment of the association between TNF-α 308 G/A polymorphism and cervical cancer risk. Electronic searches of PubMed, Embase, and Web of Science were performed for all publications on the association between TNF-α 308 G/A polymorphism and cervical cancer risk through October 26, 2012. The pooled odds ratios (ORs) with their 95 % confidence interval (95 % CIs) were calculated to assess the association. Fifteen studies with a total of 3,743 cervical cancer cases and 4,096 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with increased risk of cervical cancer under three main genetic comparison models (A vs. G, OR 1.20, 95 % CI 1.02-1.42, P=0.03; AA vs. GG, OR 1.31, 95 % CI 1.00-1.72, P=0.048; AA vs. GG/GA, OR 1.30, 95 % CI 1.00-1.71, P=0.05). Subgroup analysis by ethnicity further showed that there was a significant association between TNF-α 308 G/A polymorphism and increased risk of cervical cancer in Asians (AA vs. GG, OR 1.83, 95 % CI 1.05-3.20, P=0.034; AA vs. GG/GA, OR 1.84, 95 % CI 1.05-3.22, P=0.032). The meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with increased risk of cervical cancer, and TNF-α 308 G/A mutant allele A is a risk factor of cervical cancer.

Quantitative assessment of the association between glutathione S-transferase P1 Ile105Val polymorphism and bladder cancer risk

Previous studies investigating the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and bladder cancer risk reported controversial results. This study aimed to quantify the strength of the association between GSTP1 Ile105Val polymorphism and bladder cancer risk by performing a meta-analysis. We searched the PubMed, Embase, and Wanfang databases for publications on the association between GSTP1 Ile105Val polymorphism and bladder cancer risk. We estimated the pooled odds ratios (ORs) with their confidence intervals (95 %CIs) to assess the association. Twenty-five individual studies with a total of 12,360 subjects were finally included. Meta-analysis of all 25 studies showed that GSTP1 Ile105Val polymorphism was associated with increased risk of bladder cancer risk under four genetic comparison models (for G versus A, random-effect OR=1.19, 95 %CI 1.05-1.35; for GG versus AA, random-effect OR=1.49, 95 %CI 1.12-1.97; for GG/GA versus AA, random-effect OR=1.20, 95 %CI 1.03-1.39; for GG versus GA/AA, random-effect OR=1.41, 95 %CI 1.10-1.80). Sensitivity analysis showed that GSTP1 Ile105Val polymorphism was still associated with bladder cancer risk under three genetic comparison models (for G versus A, random-effects OR=1.13, 95 %CI 1.01-1.26; for GG versus AA, random-effects OR=1.29, 95 %CI 1.01-1.65; for GG versus GA/AA, random-effects OR=1.19, 95 %CI 1.04-1.35). No evidence of publication bias was observed. This meta-analysis shows that there is an obvious association between GSTP1 Ile105ValIle105Val polymorphism and bladder cancer risk, and GSTP1 ILE105VAL polymorphism contributes to bladder cancer risk.

A meta‐analysis of the relationship of the Parkin p.Val380Leu polymorphism to Parkinson's disease

Parkinson's disease (PD) is one of the most common movement disorders. Parkin p.Val380Leu polymorphism (c.1239G > C) has been investigated as a potential genetic hallmark of PD, but studies examining the association between the polymorphism and PD have reported conflicting results. Therefore, we conducted a meta-analysis to assess the influence of Parkin p.Val380Leu polymorphism on the susceptibility of PD. Computer and hand searches of the literature were conducted using the MEDLINE, EMBASE, Cochrane Library, and China Academic Journals databases to identify studies addressing the association between the Parkin p.Val380Leu polymorphism and PD risk. We performed analyses of study characteristics, heterogeneity, and funnel plot asymmetry in analyses analogous to additive, dominant, recessive, homozygous, and heterozygous genetic models with the odds ratio (OR) as the measure of association. A total of 11 case-control studies involving 2,073 PD cases and 2,131 controls were included. When all 11 studies were pooled into the analysis, the presence of the Leu allele at the Parkin p.Val389Leu polymorphism was associated with decreased risk for PD in three genetic comparison models: OR in additive model: 0.79, 95% confidence interval (CI) = 0.64-0.98, P = 0.029; OR in recessive model: 0.55, 95% CI = 0.35-0.89, P = 0.014; OR in homozygous model: 0.51, 95% CI = 0.32-0.82, P = 0.005. Begg's funnel plot and Egger's test provided visual and statistical evidences for funnel plot symmetry, without evidence presence of publication bias. We conclude that the presence of the Leu allele at the Parkin p.Val380Leu polymorphism is associated decreased risk for PD.

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: A meta-analysis

AimsData on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic. MethodsWe searched for case–control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated. ResultsSix case–control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72+ genotypes in Caucasians (OR=0.79, 95% CI: 0.64–0.98, Pz=0.030). ConclusionThe ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion.

Transforming Growth Factor Beta-1 C-509T Polymorphism and Cancer Risk: A Meta-analysis of 55 Case-control Studies

To investigate the association of transforming growth factor-beta 1 (TGF-β1) C-509T polymorphism and susceptibility to cancer by means of meta-analysis. An extensive search was performed to identify eligible case-control studies investigating such a link. The strength of the association between TGF-β1 C-509T polymorphism and cancer risk was assessed by pooled odds ratios (ORs) and 95%confidence intervals (95%CIs) in fixed or random effects models. 55 published case-control studies with a total number of 21,639 cases and 28,460 controls were included. Overall, there was no association between TGF-β1 C-509T and cancer risk in all genetic comparison models (TT vs. CC: OR=1.01, 95%CI=0.89-1.15; T vs. C: OR=1.01, 95%CI=0.94-1.07). However, a stratified analysis by cancer type indicated -509 T allele was significantly associated with decreased risk of colorectal cancer (CRC) (TT vs. CT/CC: OR=0.85, 95%CI=0.76-0.95), especially for Caucasians (TT vs. CT/CC: OR=0.83, 95%CI=0.71-0.98) and for population-based studies (TT vs. CT/CC: OR=0.78, 95%CI=0.68- 0.89). This meta-analysis suggested that TGF-β1 C-509T polymorphism might contribute to a decreased risk on colorectal cancer susceptibility, especially for Caucasians.

Current Evidence on VEGF+405G/C Polymorphism and Malignancy Susceptibility: A Meta-Analysis Involving 30 Studies

The association of VEGF+405G/C (where VEGF is vascular endothelial growth factor) polymorphism and malignancy susceptibility attracts considerable attention because VEGF is one of the most potent angiogenic factors and plays a critical role in the onset and development of malignancy. However, the published findings remain inconclusive. In order to derive a more precise assessment of the association, we performed a meta-analysis including 30 published case-control studies from PubMed, Embase, and Ovid databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. In the pooled analyses, no significant association was found between VEGF+405G/C polymorphism and malignancy susceptibility in different genetic models (G-allele vs. C-allele: OR=1.00, 95% CI: 0.93-1.07; CC vs. GG: OR=1.01, 95% CI: 0.88-1.15; GC+CC vs. GG: OR=1.00, 95% CI: 0.91-1.10; CC vs. GC+GG: OR=1.01, 95% CI: 0.90-1.13). When stratified by ethnicity, a weak association between this polymorphism and malignancy susceptibility was found in African under allelic frequency comparison (OR=0.65, 95% CI: 0.43-0.98) and dominant genetic model comparison (OR=1.95, 95% CI: 1.09-3.50). In summary, although our meta-analysis indicated a weak association of VEGF+405G/C polymorphism with malignancy susceptibility in African, no persuasive evidence of association between the polymorphism and malignancy susceptibility was detected in the pooled analyses. Therefore, more studies with larger scale of participants, especially Africans, are required to further evaluate gene-environment interaction on this polymorphism and malignancy susceptibility.

Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants

The association between transforming growth factor β1 (TGF-β1)-509 C>T and risk of digestive tract cancer (DTC) remained uncertain as previous studies reported conflicting results. The aim of this study was to assess the association by using a meta-analysis. The databases of MEDLINE, EMBASE and WANGFANG (Chinese database) were retrieved, and latest update was on 2nd February, 2012. Pooled odds ratio and 95% confidence interval (OR and 95% CI) were calculated by using a fixed- or random-effect model. Ultimately, twenty nine case–control studies with 8664 cases and 12,532 controls were included in this meta-analysis. Overall, there was no association between TGF-β1-509 C>T and risk of DTC in all genetic comparison models (OR and 95% CI: 0.96 and 0.81–1.15 for TT vs. CC, 0.98 and 0.91–1.05 for T carriers vs. C carriers). When subgroup analyses were conducted according to ethnicity, types of cancer and sample size, T allele was significantly associated with decreased risk of DTC for Caucasians and for large sample-sized studies, and was associated with decreased risk of colorectal cancer (OR and 95% CI for TT vs. CC: 0.82 and 0.70–0.97 for Caucasians, 0.80 and 0.68–0.98 for large sample-sized studies, 0.78 and 0.62–0.97 for colorectal cancer). This study indicated that TGF-β1-509 C>T polymorphism was probably associated with risk of DTC, especially for Caucasians. Because of modest limitation, our findings should be confirmed by future studies.

Methylenetetrahydrofolate Reductase C677T Polymorphism and Cervical Cancer Risk: a Meta-Analysis

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of MTHFR C677T polymorphism in cervical carcinogenesis is still controversial. We performed a meta-analysis of all relevant case-control studies that examined any association between the C677T polymorphism and cervical cancer risk. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess links. Finally, 10 studies with a total of 2113 cervical cancer cases and 2804 controls were included. Results from this meta-analysis showed that significantly elevated cervical cancer risk was associated with the MTHFR T allele in the Asian population under conditions of two genetic comparison models (for TT vs. CC, OR=1.37, 95%CI 1.00-1.87, P=0.050; for TT vs. TC+CC: OR=1.34, 95%CI 1.01-1.77, P=0.039). However, there was no obvious association between the MTHFR C677T polymorphism and cervical cancer risk in the other populations. The MTHFR C677T polymorphism is associated with cervical cancer risk in Asians, while any possible link in the Caucasian population needs further studies.

Pro Variant of TP53 Arg72Pro Contributes to Gastric Cancer Risk in Asians: Evidence from a Meta-analysis

Previous studies investigating the association between TP53 Arg72Pro polymorphism and gastric cancer (GC) risk in Asian population have reported controversial results. Thus, a meta-analysis was performed. A comprehensive literature search was conducted and 17 case-control studies were finally included, involving a total of 5,990 GC cases and 6,812 controls. Subgroup analyses were performed by the sample size. Meta-analysis of all 17 studies showed variant genotypes of TP53 Arg72Pro to be associated with an elevated GC risk in three genetic comparison models (OR(Pro vs. Arg)=1.13, 95%CI 1.03-1.25, P(OR)=0.01; OR(Homozygote comparison model)=1.33, 95%CI 1.07-1.64, P(OR)=0.009; OR(Dominant genetic model)=1.13, 95%CI 1.05-1.22, P(OR)=0.002). Besides, a more obvious association was observed after the heterogeneity was decreased (all P values less than 0.001). This association was further identified by both subgroup and sensitivity analyses. This meta-analysis suggests the Pro variant of TP53 Arg72Pro contributes to gastric cancer risk in Asians.

XRCC1-77T>C Polymorphism and Cancer Risk: A Meta-analysis

Variants of X-ray repair cross-complementing group 1 (XRCC1) are involved in the development of cancer, but studies investigating the association of XRCC1-77T>C polymorphism with cancer risk have reported conflicting results. To clarify the effect of the XRCC1 -77T>C polymorphism on cancer risk, we performed a meta-analysis by conducting searches of the published literature in PubMed, Embase and CBM databases. Finally, 13 studies were included into our meta-analysis, involving a total of 11, 678 individuals. Subgroup analyses were performed by ethnicity and cancer type. The results of this meta-analysis showed that there was significant association between the C variant of XRCC1-77T>C polymorphism and cancer risk in all four genetic comparison models (ORC vs. T =1.19, 95%CI 1.07-1.31, P = 0.001; OR homozygote model =1.28, 95%CI 1.07-1.52, P = 0.007; OR recessive genetic model =1.22, 95%CI 1.04-1.44, P = 0.015; OR dominant model =1.21, 95% CI 1.07-1.35, P = 0.001). In the subgroup analyses based on ethnicity, the association was still significant in the Asian population (all p values<0.001), but not in the Caucasian population (all p values > 0.05). Thus, the XRCC1 -77T>C polymorphism is associated with cancer risk, and individuals with XRCC1 -77C variant have a significantly higher cancer risk, particularly in the Asian population.

Association of CD40 Gene Polymorphisms with Sporadic Breast Cancer in Chinese Han Women of Northeast China

BackgroundBreast cancer is a polygenetic disorder with a complex inheritance pattern. Single nucleotide polymorphisms (SNPs), the most common genetic variations, influence not only phenotypic traits, but also interindividual predisposition to disease, treatment outcomes with drugs and disease prognosis. The co-stimulatory molecule CD40 plays a prominent role in immune regulation and homeostasis. Accumulating evidence suggests that CD40 contributes to the pathogenesis of cancer. Here, we set out to test the association between polymorphisms in the CD40 gene and breast carcinogenesis and tumor pathology.Methodology and Principal FindingsFour SNPs (rs1800686, rs1883832, rs4810485 and rs3765459) were genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in a case-control study including 591 breast cancer patients and 600 age-matched healthy controls. Differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed by the Chi-square test for trends. Our preliminary data showed a statistically significant association between the four CD40 gene SNPs and sporadic breast cancer risk (additive P = 0.0223, 0.0012, 0.0013 and 0.0279, respectively). A strong association was also found using the dominant, recessive and homozygote comparison genetic models. In the clinical features analysis, significant associations were observed between CD40 SNPs and lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR) and tumor protein 53 (P53) statuses. In addition, our haplotype analysis indicated that the haplotype Crs1883832Grs4810485, which was located within the only linkage disequilibrium (LD) block identified, was a protective haplotype for breast cancer, whereas Trs1883832Trs4810485 increased the risk in the studied population, even after correcting the P value for multiple testing (P = 0.0337 and 0.0430, respectively).Conclusions and SignificanceOur findings primarily show that CD40 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features among Chinese Han women from the Heilongjiang Province.

Tumour necrosis factor alpha -308G/A polymorphism and risk of the four most frequent cancers: a meta-analysis

The latest data show that breast, prostate, lung and colorectal cancer are the four most frequent cancers in both sexes worldwide. A number of molecular epidemiological studies have been conducted to examine the association between TNF alpha -308G/A and the risk of those cancers. However the results have been inconclusive or inconsistent. We then performed a meta-analysis to derive a precise estimation of this association. We carried out a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database for studies using related keywords. The inclusion criteria were (i) in English or Chinese; (ii) case-control study on this association; (iii) provide usable genotype frequencies; and (iv) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI). ORs and 95% CIs were calculated to assess the strength of this association under homozygote comparison (AA vs GG), heterozygote comparison (GA vs GG), dominant (AA/GA vs GG) and recessive (AA vs GA/GG) genetic model comparison. Thirty case-control studies with a total number of 16,507 cases and 19,749 controls were selected for analysis. Overall, no significant association was found between this polymorphism and the risk of total four cancers (GA vs GG: OR=1.02, 95% CI=0.91-1.14, P=0.78). However, there was a significant association between this polymorphism and breast cancer risk in western populations (GA vs GG: OR=0.91, 95% CI=0.85-0.96, P=0.002). This meta-analysis also revealed that this polymorphism was not associated with susceptibility to the other three cancers.

Pro variant of TP53 Arg72Pro contributes to esophageal squamous cell carcinoma risk: evidence from a meta-analysis

The TP53 Arg72Pro polymorphism has been investigated as a potential genetic hallmark of esophageal cancer, but studies investigating the association between the TP53 Arg72Pro polymorphism and esophageal cancer risk have reported conflicting results. A meta-analysis was conducted to reach a conclusion on such a possible association. Computer searches of the literature were conducted in Pubmed and Embase databases and 11 published case-control studies were finally included, involving a total of 2294 esophageal cancer cases and 4034 controls. When all 11 studies were pooled into the analysis, an increased esophageal cancer risk was significantly associated with the Pro variant of TP53 Arg72Pro in three genetic comparison models [odds ratio (OR)Pro vs. Arg=1.21, 95% confidence interval (CI): 1.05-1.39, POR=0.009; ORDominant genetic model=1.22, 95% CI: 1.09-1.37, POR=0.001; ORHomozygote model=1.40, 95% CI: 1.05-1.87, POR=0.024]. In subgroup analyses based on pathological type, the Pro variant was significantly associated with an increased esophageal squamous cell carcinoma (ESCC) risk in all four genetic comparison models (ORPro vs. Arg=1.26, 95% CI: 1.08-1.47, POR=0.003; OR Recessive genetic model=1.42, 95% CI: 1.07-1.88, POR=0.015; ORDominant genetic model=1.25, 95% CI: 1.10-1.42, POR=0.001; ORHomozygote model=1.55, 95% CI: 1.14-2.10, POR=0.005), whereas the association between TP53 Arg72Pro polymorphism and esophageal adenocarcinoma risk was still uncertain owing to the limited studies included in this meta-analysis. In addition, the association between TP53 Arg72Pro polymorphism and ESCC risk was also significant in Asians. These results suggest that the Pro variant of TP53 Arg72Pro is an important genetic hallmark contributing to ESCC risk.

Review of Pathological Hallmarks of Schizophrenia: Comparison of Genetic Models With Patients and Nongenetic Models

Schizophrenia is a condition that impairs higher brain functions, some of which are specific to humans. After identification of susceptibility genes for schizophrenia, many efforts have been made to generate genetics-based models for the disease. It is under debate whether behavioral deficits observed in rodents are sufficient to characterize these models. Alternatively, anatomical and neuropathological changes identified in brains of patients with schizophrenia may be utilized as translatable characteristics between humans and rodents, which are important for validation of the models. Here, we overview such anatomical and neuropathological changes in humans: enlarged ventricles, dendritic changes in the pyramidal neurons, and alteration of specific subtypes of interneurons. In this review, we will overview such morphological changes in brains from patients with schizophrenia. Then, we will describe that some of these alterations are already recapitulated even in classic nongenetic models for schizophrenia. Finally, in comparison with the changes in patients and nongenetic models, we will discuss the anatomical and neuropathological manifestation in genetic models for schizophrenia.

Comparison of genetic models for analysing the effects of a PvuII polymorphism in the oestrogen receptor 1 (ESR1) gene on prolificacy in an Iberian × Meishan pig population

The effect of a previously reported PvuII polymorphism in oestrogen receptor 1 (ESR1) was analysed in an F(2) population of Iberian x Meishan pigs. We tested three hypotheses: (1) that a causal mutation was fixed in the parental populations, (2) that a causal mutation existed that was in complete linkage disequilibrium with the alleles of the PvuII polymorphism and (3) that a causal mutation existed in linkage disequilibrium within each parental population. The third model was the most plausible based on the available data. ESR1 alleles displayed different patterns of linkage disequilibrium with the causal mutation in each of the parental populations and the PvuII polymorphism was clearly not the causal mutation. As a consequence, the use of the ESR1 mutation for selection must be evaluated for a particular pig population before it is applied.

Computer analysis of intraluminal pressure records.

<h3>Introduction</h3> Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082bp (rs1800896) has been associated with reduced in IL-10 production in vitro. We aimed to test the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies. <h3>Methods</h3> Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE and Scopus databases and stratified into two groups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test. <h3>Results</h3> A total of 24 studies were included for quantitative synthesis with a sample of 19,135 (11,143 cases/7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95% CI 1.02, 1.50), p= 0.03; OR 1.32 (95% CI 1.03, 1.69), p= 0.03 and OR 1.18 (95% CI 1.02, 1.36), p= 0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD (p= NS). Sensitivity analysis was performed for both subgroups across all three genetic model comparisons. Sensitivity analysis was performed where studies were excluded one after another, and the analysis was repeated after each omission. In the early or severe CAD subgroup, lower bound of the 95% CI generally remained over 1.0, indicating no significant deviation from the main association. (Figure 1, Panel A) Similarly, we observed consistency for the non-severe CAD subgroup, which remained non-significant after each omission. (Figure 1, Panel B). <h3>Conclusions</h3> IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.