Lack of association between the G+2044A polymorphism of interleukin-13 gene and chronic obstructive pulmonary disease: a meta-analysis

Numerous studies have investigated association of interleukin-13 (IL-13) G+2044A polymorphism with COPD susceptibility; however, the results were inconsistent and inconclusive. To evaluate the association between the IL-13 G+2044A polymorphism and susceptibility to COPD, a meta-analysis of published case–control studies was performed. Based on PubMed and Chinese database, this research selected studies that examined the association of the IL-13 G+2044A polymorphism with COPD. A genetic model-free approach was used to assess whether the combined data showed this association. Then a subgroup analysis was also performed, with stratifications for race, study design, and sample size. Six studies (total 1,213 COPD patients and 801 control subjects) for the IL-13 G+2044A polymorphism with COPD were included in the meta-analysis (G- vs A-allele: OR 1.12, 95 % CI 0.96–1.32, P = 0.15; genotypes GG+GA vs genotype AA: OR 0.99, 95 % CI 0.49–2.00, P = 0.98; genotype GG vs genotypes GA+AA: OR 1.18, 95 % CI 0.97–1.44, P = 0.09; genotype GA vs genotypes GG+AA: OR 0.85, 95 % CI 0.70–1.04, P = 0.11). This meta-analysis demonstrates that the IL-13 G+2044A polymorphism does not confer susceptibility to COPD. More detailed data about individual and environment, larger sample sizes with unbiased genotyping methods and matched controls in different populations are required.     

Effects of Polymorphisms -1112C/T and +2044A/G in Interleukin-13 Gene on Asthma Risk: A Meta-Analysis

Background

Associations between interleukin-13 (IL-13) polymorphisms and asthma risk remained controversial and ambiguous. Therefore, we performed a meta-analysis to assess the associations between IL-13 polymorphisms and asthma susceptibility.

Methods

Pubmed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wangfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the random-effects model.

Results

Thirty-four studies were included in this meta-analysis. The results indicated that IL13 -1112C/T polymorphism was significantly associated with asthma risk (OR = 1.20, 95% CI 1.08–1.34, P = 0.0009) in a dominant genetic model. When stratifying for race, IL13 -1112C/T polymorphism exhibited increased asthma risk in Caucasians (OR = 1.30, 95% CI 1.09–1.55, P = 0.003), while no significant association was found in Asians and African Americans. In the subgroup analysis based on atopic status, significant association was observed in atopic patients (OR = 1.25, 95% CI 1.07–1.45, P = 0.004) but not in the non-atopic patients. In addition, a significant association between IL13+2044A/G polymorphism and asthma risk was observed (OR = 1.18, 95% CI 1.08–1.28, P = 0.0002). In the subgroup analysis by ethnicity, there were significant associations between IL13+2044A/G polymorphism and asthma risk in Asians (OR = 1.19, 95% CI 1.04–1.36, P = 0.01) and Caucasians (OR = 1.22, 95% CI 1.06–1.40, P = 0.005) but not in African Americans. In the subgroup analysis stratified by atopic status, a marginal significant association was found in atopic patients (OR = 1.12, 95% CI 1.00–1.26, P = 0.05).

Conclusions

This meta-analysis suggested that the IL13 -1112C/T and +2044A/G polymorphisms were risk factors for asthma.     

Association of interleukin-8 gene polymorphisms with the risk of hepatocellular carcinoma

Interleukin-8 (IL8) polymorphisms have been implicated in several cancers, but their roles in the pathogenesis of hepatocellular carcinoma (HCC) are largely unknown. The present study was designed to explore the association between IL8 polymorphism and the risk of HCC in a Chinese population. Four single nucleotide polymorphisms (SNPs) of the IL8 gene ?251A/T, +781C/T, ?353A/T and +678T/C were analyzed in 205 HCC patients and 208 healthy controls in a Chinese population. Serum levels of IL8 were detected in HCC patients and healthy controls. The association between IL8 polymorphisms and HCC risk was measured using the adjusted odds ratios (OR) and their 95 % confidence intervals (CI) from multiple logistic regression analysis. Haplotype analysis and gene-environment interaction analysis was also performed. The serum level of IL8 was significantly higher in HCC patients compared with healthy controls (P < 0.001). After adjusting for confounding factors, no significant associations were found between ?251A/T, +781C/T, ?353A/T and +678T/C and HCC risk (all P > 0.05). Haplotype analysis showed that A²⁵¹-C⁷⁸¹-A³⁵³-C⁶⁷⁸ conferred decreased risk of HCC onset (adjusted OR 0.31, 95 % CI 0.13–0.77). No significant interaction effects were found between the four SNPs and HBV infection, cirrhosis, gender smoking and alcohol consumption (all P > 0.05). No association between ?251A/T, +781C/T, ?353A/T and +678T/C of the IL8 gene and the risk of HCC was found in this Chinese population, and the SNPs did not display any interaction with several environmental factors with regard to HCC risk. However, it appears that A²⁵¹-C⁷⁸¹-A³⁵³-C⁶⁷⁸ is perhaps a protective haplotype for HCC.     

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis

The aim of this study was to summarize results on the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism with systemic lupus erythematosus (SLE) susceptibility by using the meta-analysis. We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 17 independent studies (to June 2012) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at two polymorphic sites found in exon-1 (at +49) and the promoter region (at ?1722). The data demonstrate that the exon-1 +49 polymorphism is associated with SLE susceptibility in Asian population. The overall risk, measured by odds ratio (OR), stratification by ethnicity indicates the exon-1 +49 GG+GA genotype is associated with SLE, at least in Asians (OR = 0.85, 95 % CI = 0.73–0.99, P = 0.04 for GG+GA vs. AA; OR = 0.85, 95 % CI = 0.72–1.00, P = 0.05 for AG vs. AA). Similar trends are found in allele-specific risk estimates and disease association. Overall, there was significant association between the 1722T/C polymorphism and overall SLE risks (OR = 0.78, 95 % CI = 0.63–0.97, P = 0.04 for GG+GA vs. AA, OR = 0.87, 95 % CI = 0.76–0.99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter ?1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population.     

Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection

Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (anti-HBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre >10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre >10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs >10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0–2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6–24.9, P < 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1–0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03–0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection.     

The association between C-159T polymorphism in CD14 gene and susceptibility to tuberculosis: a meta-analysis

The association between CD14 gene C-159T polymorphism and tuberculosis (TB) susceptibility remains inconclusive. To derive a more precise estimation of the correlation, we performed a meta-analysis summarize the possible at a systematic manner. PubMed, HighWire and ScienceDirect databases covering all papers (up to November 2012) were searched. Statistical analyses were conducted by Rev-Man and STATA. Random- and fixed-effect models were used to estimate pooled odds ratios (ORs) and 95 % confidence intervals (CIs), based on between-study heterogeneity. Eight published case–control studies investigating the relationship between C-159T polymorphism in CD14 gene and TB susceptibility were included. Results showed that individuals with T allele have an increased risk of TB compared with those with C allele (OR (95 % CI) was 1.52 (1.11, 2.08) for TT vs. TC + CC, P < 0.001; 1.27 (1.01, 1.61) for T vs. C, P = 0.04). When stratified by ethnicity, variant TT homozygote carriers had an 86 % increased risk of TB in Asians (OR (95 % CI) was 1.86 (1.57, 2.20) for TT vs. TC + CC, P < 0.001), but not in Caucasians (OR (95 % CI) was TT vs. TC + CC: OR = 0.78, 95 % CI = 0.51–1.21, P = 0.61). This meta-analysis suggests that C-159T polymorphism in CD14 gene is associated with increased risk of TB, especially in Asians, but not in Caucasians.     

The polymorphisms of IL-4, IL-4R and IL-13 genes and bladder cancer risk in a Chinese population: a case-control study

Accumulating evidence suggests that inflammatory process may play a role in bladder carcinogenesis. However, the exact mechanisms of how the inflammatory factors associate with bladder cancer risk are still unknown. In this study, we explored whether polymorphisms (i.e. IL-4 C-590T, IL-4R Ile50Val, IL-4R Ser478Pro, IL-4R Gln551Arg, IL-13 C-1055T and IL-13 Arg130Gln) of IL-4, IL-4R and IL-13 genes predicted Chinese bladder cancer risk in 817 bladder cancer and 1,141 controls. Genotyping was performed by using the TaqMan method. We did not find any overall association between these single nucleotide polymorphisms (SNPs) and bladder cancer susceptibility in a Chinese population. However, in the classification and regression tree (CART) analysis, we found that carriers of IL-13 C-1055T variant genotype in smokers had a 2.57-fold increased bladder cancer risk with a 55% patient rate (OR = 2.57; 95% CI = 1.93-3.43), comparing with non-smokers. Similar result was also observed in combination of IL-13 C-1055T and IL-13 Arg130Gln in smokers. By multifactor dimensionality reduction (MDR) analysis, the best interaction model was the two-factor model that smokers with the IL-13 C-1055T genotypes were the subgroup to predict bladder cancer risk. The results suggested that the genetic variants in IL-4, IL-4R and IL-13 genes might modulate the bladder cancer risk in a Chinese population.     

Significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians

Asthma is a complex multifactorial disorder and its management requires a better understanding of its various pathogenesis and mechanisms. Previous studies assessing the association between glutathione S-transferase T1 (GSTT1) null genotype and asthma risk during childhood reported conflicting results. To get a more precise estimation of the association between GSTT1 null genotype and risk of asthma during childhood, we performed a meta-analysis of 16 studies with a total of 18,558 subjects. Subgroup analyses were performed by ethnicity. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI) was used to assess the association. Overall, there was a significant association between GSTT1 null genotype and increased risk of children asthma (OR = 1.25, 95 % CI, 1.02–1.54; P = 0.032). Subgroup analyses showed GSTT1 null genotype was associated with increased risk of children asthma in Caucasians (OR = 1.46, 95 % CI, 1.04–2.03; P = 0.027), but not in Asians (OR = 1.03, 95 % CI, 0.55–1.94; P = 0.928) and Africans (OR = 1.33, 95 % CI, 0.92–1.91; P = 0.127). There was no evidence of publication bias in the subgroup analysis of Caucasians. In conclusion, there is a significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians. More well-designed epidemiological studies are needed to further assess this association in Asians and Africans.     

Association of TGF-β1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis

Many case–control studies have investigated the role of TGF-β1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95 % confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-β1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR = 0.65, 95 % CI = 0.48–0.88, P = 0.005; CC vs. CT + TT: OR = 0.56, 95 % CI = 0.45–0.69, P = 0.000; C vs. T: OR = 0.81, 95 % CI = 0.71–0.93, P = 0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-β1 +869C/T promoter polymorphism and RA, especially in Asian population.     

Association of the interleukin 15 (IL-15) gene polymorphisms with the risk of developing ulcerative colitis in Mexican individuals

Interleukin 15 (IL-15) is a Th1-related cytokine that triggers inflammatory cell recruitment with implications for pathogenesis in ulcerative colitis. The IL-15 gene is located within a 35 kb region of the q28-31 locus of chromosome 4. In the present work, the role of IL-15 gene polymorphisms as susceptibility markers for UC was evaluated. Seven polymorphisms of IL-15 (rs3806798, rs10833, rs4956403, rs2254514, rs2857261, rs10519613, and rs1057972) were genotyped by 5′ exonuclease TaqMan genotyping assays in a group of 199 Mexican patients with UC and 698 Mexican Mestizo healthy unrelated individuals. UC patients and healthy controls showed similar distribution of the rs3806798, rs10833, rs4956403, rs2857261, rs10519613, and rs1057972 polymorphisms. The rs2254514 polymorphism was significantly associated with decreased risk of UC as compared to controls under both dominant and additive models (OR 0.62, P_dom = 0.014 and OR 0.65, P_add = 0.02). The rs2254514 CC genotype was associated with young age at diagnosis <40 years (P = 0.03; OR 3.67). Five polymorphisms (rs1051613, rs2254514, rs2857261, rs1057972, and rs10833) were in strong linkage disequilibrium and were included in six haplotypes: H1 (ACAAC), H2 (CCGTC), H3 (CTAAT), H4 (CCAAT), H5 (CTAAC), and H6 (CCAAC). UC patients showed an increased frequency of the H6 haplotype (P = 0.005; OR 3.2) and a decreased frequency of the H5 haplotype (P = 0.031; OR 0.40). These results suggest that the IL-15 rs2254514 polymorphism might have an important role in the development of UC in the Mexican population. We were able to distinguish one risk and one protective uncommon haplotype for the development of UC.     

The association between CD14 gene C-260T polymorphism and coronary heart disease risk: a meta-analysis

Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary heart disease (CHD), thrombus formation, and myocardial infarction (MI). A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with CHD. To investigate this inconsistency, we performed a meta-analysis of 28 studies involving a total of 13,335 CHD cases and 7,979 controls for C-260T of the CD14 gene to evaluate the effect of CD14 on genetic susceptibility for CHD. An overall random effects odds ratio of 1.24 (95 % CI: 1.12–1.36, P < 10^?5) was found for T allele. Significant results were also observed using dominant (OR = 1.34, 95 % CI: 1.17–1.54, P < 10^?4) or recessive genetic model (OR = 1.25, 95 % CI: 1.10–1.41, P = 0.0004). There was strong evidence of heterogeneity (P < 10^?5), which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant results were found in East Asians; whereas no significant associations were found among Caucasians and other ethnic populations in all genetic models. In the stratified analysis according to sample size, CHD endpoints, and HWE status, significantly increased risks for the polymorphism were found in all genetic models. In conclusion, our results indicate that the CD14 C-260T polymorphism is a risk factor of CHD, especially in East Asians. However, additional very large-scale studies are warranted to confirm our results.     

VEGF +936C/T and +460C/T gene polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the VEGF +936C/T (rs833061) and +460C/T (rs3025039) gene polymorphisms and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, we performed a meta-analysis. The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for case–control studies that were published up to January 2013. Data were extracted and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Ultimately, six studies were included, comprising 1006 oral cancer cases and 1016 controls. Overall, the pooled OR for VEGF +936 T allele carriers (TC + TT) versus the wild-type homozygotes (CC) was 1.28 (95 % CI 1.04–1.58; P = 0.228 for heterogeneity), the pooled OR for TT versus CC was 1.64 (95 % CI 1.34–1.98; P = 0.315 for heterogeneity), and the pooled OR for the T allele versus the C allele was 1.42 (95 % CI 1.22–1.76; P = 0.286 for heterogeneity). In the stratified analysis by ethnicity, significant risks were found among Caucasians but not Asians. However, there were no associations between VEGF +460C/T and oral cancer risk in only two of the included studies. In conclusion, this meta-analysis demonstrates that the VEGF +936 T allele may be associated with an increased risk of oral cancer, especially among Caucasian populations.     

Quantitative analysis of the association between interleukin-10 1082A/G polymorphism and susceptibility to sepsis

There are some epidemiological studies investigating the association between interleukin-10 (IL-10) 1082A/G polymorphism and sepsis susceptibility reporting conflicting findings. Our work tried to further quantitatively assess the association of the IL-10 1082A/G polymorphism with sepsis susceptibility through a systematic review and meta-analysis. A total of eleven studies with 2,528 subjects were finally included into the meta-analysis. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity among the included studies. Meta-analysis of all 11 studies showed that there was an obvious association between IL-10 1082A/G polymorphism and sepsis susceptibility under the allele comparison model (G vs A) and the codominant model (GG vs AA) (for G vs A: OR = 0.83, 95 % CI 0.72–0.96, P = 0.011; for GG vs AA: OR = 0.67, 95 % CI 0.47–0.96, P = 0.029). Subgroup analysis by ethnicity showed that there was an obvious association between IL-10-1082A/G polymorphism and sepsis susceptibility in Asians under three comparison models (for G vs A: OR = 0.75, 95 % CI 0.62–0.91, P = 0.004; for GG vs AA: OR = 0.39, 95 % CI 0.21–0.73, P = 0.003; for GG vs AA/AG: OR = 0.36, 95 % CI 0.14–0.92, P = 0.032), but there was no similar association in Caucasians under all four comparison models. Our meta-analysis reveals that the IL-10-1082A/G polymorphism has an association with the susceptibility to sepsis in Asian populations. Further studies are needed to investigate the effect of IL-10-1082A/G polymorphism on sepsis susceptibility in Caucasians.     

Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis

This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.     

The interleukin-4 − 589C/T polymorphism and the risk of asthma: A meta-analysis including 7345 cases and 7819 controls

Background

A number of studies assessed the association of − 589C/T polymorphism in the promoter region of interleukin-4 (IL-4) with asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to investigate the association between polymorphism in the IL-4 and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, 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 associations.

Results

Thirty-four studies involving 7345 cases and 7819 controls were included. Overall, significant association between − 589C/T polymorphism and asthma was observed for TT + CT vs. CC (OR = 1.26; 95% CI 1.12–1.42; P = 0.0001; I² = 26%). In the subgroup analysis by ethnicity, significant associations were found among Asians (OR = 1.36; 95% CI 1.07–1.73; P = 0.01; I² = 0%) and Caucasians (OR = 1.30; 95% CI 1.09–1.54; P = 0.004; I² = 53%) but not among African Americans (OR = 1.20; 95% CI 0.72–2.00; P = 0.48; I² = 48%). In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR = 1.20; 95% CI 0.92–1.34; P = 0.27; I² = 6%) and non-atopic asthma patients (OR = 0.97; 95% CI 0.73–1.28; P = 0.81; I² = 0%).

Conclusions

This meta-analysis suggested that the IL-4 − 589C/T polymorphism was a risk factor of asthma.     

IL-6 gene polymorphisms and CAD risk: a meta-analysis

The potential relationship between Interleukin-6 (IL-6) gene polymorphisms and coronary artery disease (CAD) has been widely investigated. However, study findings on the ?174 G/C and ?572 G/C variants remain inconsistent and somewhat controversial. The present meta-analysis was conducted in an attempt to provide a more robust synthesis conclusion. PubMed and Embase were used to search for all relevant studies published on or before May 22, 2012. A total of 19 studies were ultimately included in the analysis. Overall combined risk was calculated with fixed or random-effects models. Subgroup and sensitivity analyses were performed. Among the included studies, no statistically significant differences were found between controls and CAD cases for the G allele contrasts of the ?174 G/C and ?572 G/C polymorphisms. The co-dominant genetic model was evaluated for the ?174 G/C polymorphism. A significant association was detected using GG versuss CC (OR = 0.801, 95 % CI: [0.652, 0.983], P = 0.034). However, the association was not obviously in subgroup analysis by ethnicity. The recessive genetic model was evaluated for the ?572 G/C polymorphism. The relationship between ?572 G/C polymorphism and CAD risk was only found to be significant in Asian populations (random-effects: OR = 1.908, 95 % CI: [1.016, 3.581], P = 0.044) using GG versus GC+CC. No obvious publication bias was found by Begg’s funnel plots and the Egger’s linear regression test (P = 0.315 for ?174 G/C polymorphism and P = 0.118 for ?572 G/C polymorphism). Our study indicated that the association between the IL-6 gene and CAD risk was mild and moderate for the ?174 G/C and ?572 G/C polymorphisms. However, this relationship requires additional investigation through well-designed studies with larger sample sizes.     

Meta-analysis of the association between common interleukin-1 polymorphisms and dental implant failure

Interleukin-1 (IL) plays a pivotal role in immune–inflammatory response that maintains periodontal homeostasis. A number of epidemiological studies have been conducted to investigate the associations between common polymorphisms of IL-1 (IL-1A, IL-1B) genes and risk of peri-implant disease, but the findings remain inconclusive. Thirteen studies evaluating the association between IL-1 polymorphisms and risk for peri-implant diseases (implant failure/loss, peri-implantitis) were included. Fixed model or random-effects models were applied to calculate overall and ethnicity-specific summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) as risk estimates for IL-1 polymorphisms individually or in combination. Heterogeneity and publication bias were evaluated by Q-test, I ² statistic, Begg’s funnel plot and Egger’s test accordingly. The composite genotype of IL-1A (?889) and IL-1B (+3954) was associated with increased risk of implant failure/loss (OR 1.76, 95 % CI 1.21–2.57) and peri-implantitis (OR 2.34, 95 % CI 1.03–5.33). The significance was borderline in European descents (implant failure/loss: OR 1.48, 95 % CI 0.99–2.22; peri-implantitis: OR 1.65, 95 % CI 1.00–2.73). T allele of IL-1B (?511) was associated with increased risk of implant failure/loss (OR 1.28, 95 % CI 1.01–1.62), while the association was not significant in European descents (OR 1.12, 95 % CI 0.85–1.48). These findings support a potential role of IL-1 polymorphisms, particularly the composite genotype of IL-1A (?889) and IL-1B (+3954), in peri-implant disease susceptibility. More studies with large sample size are needed to validate the associations.     

Association of ADAM33 gene polymorphisms with psoriasis in a northeastern Chinese population

Psoriasis (PS) is a common hyperproliferative and chronic inflammatory disease of the skin. It is influenced by both genetic and environmental factors. The ADAM33 (a disintegrin and metalloproteinase 33) gene located on chromosome 20p13, has recently been identified as an asthma-susceptibility gene by positional cloning. Recently, ADAM33 has been suspected to be associated with PS. To study the association between ADAM33 and PS in the northeastern Chinese population. A total of 240 PS patients and a control group of 237 healthy volunteers were recruited for this study. Five polymorphic loci (V4, T+1, T2, T1, S2) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction–restriction fragment length polymorphism method. We observed the frequency of the rs2787094 C allele was significantly higher in cases than in controls (50 vs. 33 %, P < 0.0001).Similarly, the rs528557 C allele exhibited a significantly increased frequency in PS patients compared with healthy controls (35 vs. 21 %, P < 0.0001). We also found that the frequencies of H3 (CGGAC), H6 (CGGGG) haplotypes were significantly higher in the case group than in the control group (P = 0.006, 0.028, respectively). In contrast, the haplotype H9 (GAAAG) was more common in the control group than in the case group (P = 0.018). Our data suggest that the ADAM33 polymorphisms may be associated with PS in the northeastern Chinese population.     

Association between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether the three functional interleukin-18 (IL-18) promoter ?607 C/A (rs1946518), ?137 G/C (rs187238), and ?1297 C/T (rs360719) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. Meta-analysis was conducted on the associations between these IL-18 polymorphisms and SLE using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 11 comparisons (nine studies) involving 8,453 subjects (2,928 SLE patients and 5,525 controls) were included in the meta-analysis. In all study subjects, meta-analysis showed no association between SLE and the IL-18 ?607 C allele (odds ratio [OR] = 1.065, 95 % confidence interval [CI] = 0.870–1.303, p = 0.541). However, stratification by ethnicity indicated a significant association between this allele and SLE in Europeans (OR = 0.864, 95 % CI = 0.757–0.986, p = 0.031), but not in Asians (OR = 1.230, 95 % CI = 0.902–1.676, p = 0.190). Meta-analyses showed the same pattern for the IL-18 ?607 C allele using the dominant and additive models. Meta-analysis of the IL-18 ?137 G/C polymorphism showed no association between SLE and the IL-18 ?137 G allele in all study subjects (OR = 0.916, 95 % CI = 0.836–1.003, p = 0.057), but stratification by ethnicity indicated a significant association between this allele and SLE in Asians (OR = 0.792, 95 % CI = 0.629–0.997, p = 0.047), but not in Europeans (OR = 0.930, 95 % CI = 0.839–1.032, p = 0.171). Furthermore, meta-analysis showed that the IL-18 ?1297 C allele was significantly associated with SLE in all study subjects and in Europeans (OR = 1.240, 95 % CI = 1.052–1.482, p = 0.010 and OR = 1.303, 95 % CI = 1.050–1.617, p = 0.016). This meta-analysis shows that the IL-18 ?607 C/A and ?1297 C/T polymorphism are associated with the development of SLE in Europeans, and the IL-18 ?137 G/C polymorphism is associated with SLE in Asians.