Association between IL-6 polymorphisms and sepsis.

Allergic rhinitis (AR) is a chronic inflammatory disease of nasal mucosa. Loss of function of Th17 cells and regulatory T (Treg) cells plays a role in the pathogenesis of AR. IL18, FOXP3, and IL13 are key genes in the development of AR. However, the genetic associations between IL18, FOXP3 and IL13 genes polymorphisms and AR risk were inconclusive yet. A meta-analysis was performed by searching through Pubmed, EMBASE, web of science and CNKI databases. The ORs and 95%CIs were used to assess the genetic association between the allelic, dominant and recessive models of IL18, FOXP3 and IL13 genes polymorphisms and AR risk. A total of 15 articles (6 for FOXP3, 5 for IL18, and 5 for IL13) were enrolled in the present study. No association was detected between the IL18 rs187238, rs1946518, rs360721, FOXP3 rs2232365, rs3761548 and IL13 rs1800925 polymorphisms and AR risk (p > 0.05). Significant associations were observed between the allelic (p = 0.001, OR 1.32, 95% CI 1.12-1.56), dominant (p = 0.005, OR 1.43, 95% CI 1.11-1.83) and recessive models (p = 0.01, OR 1.64, 95% CI 1.13, 2.40) of IL13 rs20541 and AR risk. Subgroup analysis based on ethnicity revealed that the IL13 rs20541 was significantly associated with AR risk in Asian population (allelic model: p = 0.009, OR 1.36, 95% CI 1.13-1.63, dominant model: p = 0.005, OR 1.43, 95% CI 1.11-1.83; recessive model: p = 0.01, OR 1.64, 95% CI 1.13-2.40). IL13 rs20541 may contribute to the risk of AR in Asian population. To confirm these results, larger number of case-control study with more subjects is necessary in the future.

To investigate the association between IL-18 polymorphisms and Tuberculosis(TB). We searched PubMed and Embase databases, and conducted a meta-analysis using 4 models. Data were extracted from the studies by two independent reviewers. Statistical analysis was performed using STATA 12.0 software. Five qualified studies with a total of 1293 TB patients and 1724 controls were included. There was no significant association between the IL-18 -607C>A polymorphism and TB risk in the total population(AA vs CC: OR=1.27,95% CI=0.82-1.96;-CA vs CC:OR=1.06,95% CI=0.89-1.26; Dominant model: OR =1.09, 95% CI =0.83-1.43; Recessive model:OR=1.23, 95% CI=0.92-1.65). For IL-18 -137G>C polymorphism, lack of an association was also found(GG vs CC: OR=1.42,95% CI=0.78-2.58;GC vs CC:OR=1.16,95% CI=0.62-2.16; Dominant model: OR =1.34,95% CI=0.74-2.43;Recessive model:OR=0.96,95%-CI=0.26-3.56). The present meta-analysis found no evidence for IL-18 -607C>A and -137G>C polymorphisms as risk factors for TB. Further large-scale and well-designed articles are still needed to validate this result.

The objective of this study was to explore the association between transformation growth factor beta 1 (TGF-β1) gene polymorphisms and different types of arthritis. PubMed, Medline, Web of Science, Cochrane Library, Biosis and four Chinese databases: China Biology Medicine, China National Knowledge Infrastructure, Wanfang and CQVIP, were searched. Studies that analyzed the association of the TGF-β1 polymorphisms with different types of arthritis were included. OR, 95% confidence interval and P value were calculated in three models including allele, dominant and recessive models, using D + L method. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. TGF-β1 869T > C polymorphism was significantly associated with rheumatoid arthritis (RA) in allele and recessive models, but not in dominant model (allele model T vs. C: OR = 1.30, 95% CI = 1.13-1.49, P < 0.001; recessive model CC vs. TT + TC: OR = 0.57, 95% CI = 0.43-0.76, P < 0.001; dominant model TT vs. TC + CC: OR = 1.20, 95% CI = 0.99-1.45, P = 0.063). Additionally, allele and recessive models showed that TGF-β1 -509C > T was significantly correlated with RA susceptibility, while dominant model revealed nonsignificant correlation (allele model: C vs. T: OR = 1.51; 95% CI = 1.00-2.28; P = 0.049; recessive model: TT vs. CC + TC: OR = 0.52, 95% CI = 0.37-0.72, P = 0.000; dominant model: CC vs. TT + TC: OR = 1.48; 95% CI = 0.79-2.76; P = 0.223). However, no significant association was found between TGF-β1 polymorphisms and ankylosing spondylitis (AS) or osteoarthritis (OA) risk. This study demonstrated that 869T > C, -509 C > T polymorphisms of TGF-β1 gene were associated with increased susceptibility of RA, while polymorphisms of TGF-β1 gene were not associated with OA and AS. These findings suggest that studying TGF-β1 genotype may be useful in the prevention and management of RA. However, more studies are needed to evaluate the association of TGF-β1 gene polymorphisms with the susceptibility of OA and AS.

BackgroundPeriodontitis is a major oral health problem and it is considered as one of the reasons for tooth loss in developing and developed nations. The objective of the current review was to investigate the association between IL10 polymorphisms − 1082 A > G (rs1800896), -819C > T (rs1800871), − 592 A > C (rs1800872) and the risk of either chronic periodontitis or aggressive periodontitis.MethodsThis is a meta- analysis study, following the preferred reporting items for systematic reviews and meta- analyses (PRISMA). Relevant studies were searched in the health related electronic databases. Methodological quality of the included studies were assessed using the Newcastle-Ottawa Scale. For individual studies, odds ratio (OR) and its 95%confidence interval (CI) were calculated to assess the strength of association between IL10 polymorphisms (− 1082 A > G, -819C > T, − 592 A > C) and the risk of periodontitis. For pooling of the estimates across studies included, the summary OR and its 95% CIs were calculated with random-effects model. The pooled estimates were done under four genetic models such as the allelic contrast model, the recessive model, the dominant model and the additive model. Trial sequential analysis (TSA) was done for estimation of the required information size for this meta-analysis study.ResultsSixteen studies were identified for this review. The included studies were assessed to be of moderate to good methodological quality. A significant association between polymorphism of IL10–1082 A > G polymorphism and the risk of chronic periodontitis in the non-Asian populations was observed only in the recessive model (OR,1.42; 95% CI:1.11, 1.8,I2: 43%). The significant associations between − 592 A > C polymorphism and the risk of aggressive periodontitis in the non-Asian populations were observed in particular genetic models such as allele contrast (OR, 4.34; 95%CI:1.87,10.07,I2: 65%) and recessive models (OR, 2.1; 95% CI:1.16, 3.82,I2: 0%). The TSA plot revealed that the required information size for evidence of effect was sufficient to draw a conclusion.ConclusionsThis meta-analysis suggested that the IL10–1082 A > G polymorphism was associated with chronic periodontitis CP risk in non-Asians. Thus, in order to further establish the associations between IL10 (− 819 C > T, − 592 A > C) in Asian populations, future studies should include larger sample sizes with multi-ethnic groups.

Objectives: Previous published data indicated that interleukin-21 (IL-21) gene polymorphisms were shown to associate with multiple autoimmune diseases (ADs), but the results remain inconclusive. The aim of this study was to perform a meta-analysis to assess the overall association between IL-21 gene polymorphisms (rs907715, rs2221903) and multiple ADs. Methods: All eligible case–control studies were searched in the PubMed and Embase database. A meta-analysis was conducted on the association between the IL-21 gene variants and ADs using: (1) allelic contrast, (2) homozygote contrast, (3) the recessive model, and (4) the dominant model. Results: A total of 12 relevant studies including 10 535 cases and 19 356 controls were enrolled in this meta-analysis. A significant association between IL-21 rs907715 gene polymorphism and AD was found under the allelic (OR: 1.102, 95% CI: 1.057–1.149, p = 0.000), homozygous (OR: 1.220, 95% CI: 1.089–1.368, p = 0.001), dominant (OR: 1.160, 95% CI: 1.027–1.309, p = 0.017), and recessive genetic model (OR: 1.119, 95% CI: 1.055–1.187, p = 0.000) among Caucasian populations. However, there was no significant association between IL-21 rs2221903 polymorphism and AD in different genetic models. Conclusions: Data from the present study suggest that the IL-21 rs907715 polymorphism might be associated with multiple ADs susceptibility in Caucasians. Especially, the allele G of intronic rs907715 in IL-21 confers increased risk of ADs.

A systematic review and meta-analysis were conducted to find out if there was association between Plasminogen Activator Inhibitor-1 (PAI-1) gene polymorphisms (- 844 G > A and - 675 4G > 5G) and susceptibility to coronary artery disease (CAD). Search of electronic databases was performed and the pooled odds ratio (OR) and 95% confidence interval (CI) were exerted to evaluate the pooled association between the single-nucleotide polymorphisms (SNPs) and risk of CAD. For - 675 4G > 5G SNP, dominant (OR = 0.90), recessive (OR = 0.90), allelic (OR = 0.91), homozygous (OR = 0.84), and heterozygous (OR = 0.96) models were significantly associated with decreased risk of CAD. Moreover, all five genetic models were associated significantly with decreased CAD risk in the Causation and Arab populations. The results in Asians were marginally significant in recessive, allelic, and homozygote models. The male gender was found to be a risk factor in individuals with PAI-1 4G > 5G SNP in the dominant model (OR = 0.89), recessive model (OR = 0.91), allelic model (OR = 0.92), homozygous model (OR = 0.86), and heterozygous model (OR = 0.91). The results of pooled ORs for overall populations and subgroup analysis by ethnicity reject any association between PAI-1 gene - 844 G > A polymorphism and CAD risk under all genetic comparisons. The results of this meta-analysis indicated that PAI-1 4G > 5G SNP was associated with decreased risk of CAD in the overall population as well as in the Asians, Caucasians, and Arab populations. However, the PAI-1 gene - 844 G > A polymorphism had no significant association with susceptibility to CAD.

The associations between IL-6 gene single nucleotide polymorphisms (SNPs) and risk of hepatocellular carcinoma (HCC) are controversial. We performed a meta-analysis to provide more credible evidence. We searched for relevant studies published up to 2013 by performing an efficient searching strategy. Odds ratios (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the associations between IL-6 polymorphisms and HCC risk. We identified eight case-control studies involving 1,448 HCC cases and 3,160 controls. Our estimation specifically focused on two SNPs of the IL-6 gene, -174 G/C and -572 G/C. The combined results showed that association between IL-6-174 G/C polymorphism and risk of HCC was significant under additive model (CC vs. GG: OR 0.36; 95% CI, 0.16, 0.85) and recessive model (GG+CG vs. CC: OR 2.82; 95% CI 1.26, 6.28). However, the IL-6-572 G/C polymorphism was not associated with HCC risk. In conclusion, IL-6-174 G/C, but not -572 G/C polymorphism could be a candidate for susceptibility to HCC. However, the results should be cautiously interpreted due to the limited number of the included studies.

A meta-analysis was conducted to determine the significant risk alleles which increase the risks of gestational diabetes mellitus (GDM) in Asian to help in decision-making for genotyping of women at risk. PubMed, Science Direct and HuGE navigator were used to identify relevant studies from January 2000 to November 2018. Data extraction was done by five reviewers. Using Review Manager 5.3, association between 11 SNPs and risks of GDM was determined. Odds ratios (ORs) with 95% confidence intervals (95% CI), test of heterogeneity and publication bias were calculated. The result was considered significant if p-value ≤ 0.05. Twenty-one studies were identified based on the inclusion and exclusion criteria. From 11 genetic variants studied, 9 were found to have significant association with GDM susceptibility with different heterogeneity. Allelic, dominant and recessive genetic models show MTNR1B (rs138753, rs10830963) and CDKAL1 (rs7754840) are significantly associated with GDM. IGF2BP2 (rs4402960) was found to have significant association with GDM using allelic and recessive models. For TCF7L2 (rs7903146), significant association was found using allelic, dominant and over dominant models. KCNQ1 (rs2237892) showed association with GDM in dominant model only. Strong associations with increased susceptibility for GDM were also found for GSTM1 (deletion), GSTT1 (deletion) and GSTP1 (rs1695). However, MTNR1B (rs10830962) and PPARγ2 are lack of association with GDM risk in Asian population. Nine genetic variants were associated with increased GDM risk in Asian population. Screening of these polymorphisms to identify pregnant women at risk is recommended for prevention and personalised intervention.

Mannose-binding lectin (MBL), an essential innate immune molecule, enhances the opsonization process and activates the complement system. Genetic variations at the promoter and coding region of the MBL-2 gene have been associated with susceptibility to systemic lupus erythematosus (SLE); however, reports remained inconsistent. The present study performs a meta-analysis of published peer-reviewed articles to draw a definitive conclusion. Published peer-reviewed articles on the association of MBL-2 gene polymorphisms and SLE were screened on various databases such as PubMed (Medline), ScienceDirect, and Google Scholar. A total of 23 eligible articles were included in the present study, comprising 3074 SLE patients and 3985 controls. Genotype and/or allele data for MBL-2 polymorphisms (A > B, A > C, A > D, A > O, Y > X and H > L) were extracted and analyzed by Comprehensive Meta-Analysis software (CMA V3.1). The overall analysis revealed a significant association of MBL-2 (A > O) polymorphism with a predisposition to SLE in allele contrast (p = 0.000; OR = 1.261), homozygous (p = 0.005; OR = 1.482), heterozygous (p = 0.004; OR = 1.247), dominant (p = 0.000; OR = 1.303) and recessive (p = 0.025; OR = 1.356) genetic comparison model. Similar results were also observed in the comparison of allele and the dominant genetic model of MBL-2 (A > B) polymorphism in overall (allele: p = 0.000, OR = 1.46, dominant: p = 0.001, OR = 1.31) and in the Asian cohorts (allele: p = 0.007, OR = 1.43, dominant: p = 0.008, OR = 1.32). Interestingly, MBL-2 (Y-221X) polymorphism exhibited protection against the development of SLE in heterozygous (p = 0.005, OR = 0.619) and dominant genetic comparison (p = 0.01, OR = 0.672) models. MBL-2 variants (A > O and A > B) are associated with predisposition to SLE. Conversely, promoter polymorphism (Y-221X) offers protection against SLE development.

Genetics of Schizophrenia and the New Millennium: Progress and Pitfalls

BackgroundIncreasing evidence shows that polymorphisms in a number of genes can influence age-related macular degeneration (AMD) risk. This study aimed to investigate the association of CX3CR1 839C/T, CX3CR1 745G/A, PLEKHA1 958A/G, VEGFA +674C/T, and VEGFA +936C/T polymorphisms with AMD risk among Chinese.Material/MethodsThe polymorphisms were genotyped on 827 AMD patients and 827 controls, and the odds ratios (ORs) were calculated under allele, additive, recessive, and dominant genetic models. Logistic regression analysis was performed to control for potential confounders (age, sex, and smoking status).ResultsWe showed that all the 5 polymorphisms showed a significant association with AMD risk under the additive model (for homozygous mutant genotype) and at least 1 other genetic model, both before and after adjustment for the potential confounders. PLEKHA1 958A/G polymorphism was associated with a decreased AMD risk (additive model: aOR=0.722, 95% CI=0.450–0.979, P=0.019; allele model: aOR=0.883, 95% CI=0.736–0.992, P=0.014), while all other polymorphisms were associated with an increased AMD risk (CX3CR1 839C/T, additive model: aOR=2.682, 95% CI=1.119–5.709, P=0.022, recessive model: aOR=2.729, 95% CI=1.141–6.048, P=0.010; CX3CR1 745G/A, additive model: aOR=2.614, 95% CI=1.231–6.012, P=0.020, recessive model: aOR=2.340, 95% CI=1.227–5.993, P=0.011; VEGFA +674C/T, additive model: aOR=1.601, 95% CI=1.253–2.179, P<0.001, dominant model: aOR=1.287, 95% CI=1.058–1.570, P<0.001, allele model: OR=1.220, 95% CI=1.118–1.427, P<0.001; VEGFA +936C/T, additive model: aOR=1.509, 95% CI=1.105–2.311, P<0.001, recessive model: aOR=1.432, 95% CI=1.027–2.192, P=0.009, dominant model: aOR=1.207, 95% CI=1.031–1.514, P0.001, allele model: aOR=1.216, 95% CI=1.062–1.408, P<0.001).ConclusionsWe conclude that the 5 polymorphisms could serve as biomarkers for AMD susceptibility.

Recent studies have shown that long noncoding RNAs (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) polymorphisms are associated with cancer susceptibility. The greatest threat to women's health among avariety of cancers is breast cancer (BC), cervical cancer (CC), and ovarian cancer (OC), and the incidence of it is increasing. We performed a meta-analysis to clarify the relationship between lncRNA HOTAIR expression and BC, CC, and OC susceptibility. We thoroughly searched PubMed, Embase, and the Cochrane Library to obtain the relevant literature. We extracted data from case groups and control groups for each single-nucleotide polymorphism (SNP) (rs4759314, rs920778, rs189663, rs12826786, rs7958904, and rs874945) and compared the relationship between alleles, codominance models, dominant and invisible models and BC, CC, and OC susceptibility. Our study included 11 studies with a total of 5322 patients. There was a significant association between the rs4759314 polymorphism of HOTAIR and susceptibility to BC, CC, and OC (codominant model: AG/AA odds ratio [OR] = 1.13 [95% confidence intervals [CI], 1.00-1.29], GG/AA OR = 1.54 [95% CI, 1.06-2.23]; dominant model: GG + AG/AA OR = 1.16 [95% CI, 1.02-1.32]; and recessive model: GG/AA + AG OR = 1.51 [95% CI, 1.05-2.19]). The association between the expression of rs920778 and BC, CC, and OC susceptibility was not clear (alleles T/C: OR = 1.28 [95% CI, 0.87-1.89]; in codominant model: CT/CC OR = 1.10, [95% CI, 0.71-1.71], TT/CC OR = 1.29 [95% CI, 0.59-2.80]; dominant model: TC + TT/CC OR = 1.16, [95% CI, 0.73-1.86]; and recessive model: TT/TC + CC OR = 1.43, [95% CI, 0.83-2.47]). HOTAIR polymorphism rs1899663 was associated with BC, CC, and OC susceptibility to a certain extent, (alleles T/G OR = 0.90 [95% CI, 0.69-1.16]; in the codominant model: GT/GG OR = 0.81 [95% CI, 0.50-1.30], TT/GG OR = 1.04 [95% CI, 0.63-1.72]; dominant model: GT + TT/GG OR = 0.82 [95% CI, 0.52-1.29]; and recessive model: TT/GT + GG OR = 1.21 [95% CI, 0.76-1.94]). The rs12826786, rs7958904, and rs874945 polymorphisms were associated with a certain degree of BC, CC, and OC susceptibility, but they were not statistically significant. HOTAIR rs4759314 increased susceptibility to BC, CC, and OC in some patients; rs029778 and rs1899663 also increased susceptibility to some extent. SNPs rs12826786, rs7958904, and rs874945 did not correlate with an effect on patient susceptibility to BC, CC, and OC.

Response to Zang et al. and Han et al.

The aim of this study was to investigate the association of two common interleukin 12B (IL-12B) polymorphisms (rs3212227 and rs6887695) with rheumatoid arthritis (RA) susceptibility through meta-analyses. A systematic literature search of PubMed, Web of Science, Cochrane Library, and Embase databases was conducted on articles published before 28 February 2016. Then odds ratio (OR) with 95% confidence interval (CI) was used to quantify the strength of association for homozygote, heterozygote, dominant, and recessive genetic models. Nine articles with a total of 17 case-control studies (12 for IL-12B rs3212227 polymorphism and 5 for IL-12B rs6887695 polymorphism) met our inclusion criteria. The pooled results demonstrated that IL-12B rs3212227 (homozygote model: OR = 0.96, 95% CI = 0.81-1.15; heterozygote model: OR = 1.07, 95% CI = 0.93-1.23; dominant model: OR = 1.05, 95% CI = 0.91-1.20; recessive model: OR = 0.93, 95% CI = 0.79-1.10) and rs6887695 (homozygote model: OR = 1.01, 95% CI = 0.84-1.21; heterozygote model: OR = 1.14, 95% CI = 0.86-1.51; dominant model: OR = 1.14, 95% CI = 0.87-1.48; recessive model: OR = 1.01, 95% CI = 0.85-1.21) polymorphisms may not be associated with RA risk. Our meta-analyses demonstrated that IL-12B rs3212227 and rs6887695 polymorphisms do not confer susceptibility to RA.

Recently, several institutions have investigated the associations of MMP-3-1171 5A/6A and IL-6-174-G/C gene polymorphisms with adolescent idiopathic scoliosis (AIS), while reports from different institutions are not consistent. Therefore, we, comprehensively and systematically performed this meta-analysis to detect whether the two gene polymorphisms are correlated with AIS. From January 1994 to October 2015, all case-control studies focussed on the relationship between the two aforementioned gene polymorphisms and the susceptibility to AIS were retrieved from bibliographic databases. A total of 16 articles were found, of which five consisted of 944 cases and 1177 controls, were finally included after being assessed by two reviewers. We calculated the pooled odds ratio (OR) with 95% confidence interval (95% CI) to assess the associations. The pooled data analyses were based on allele contrast, homozygote, heterozygote, dominant and recessive models. Overall, there was no significant association of IL-6-174-G/C gene polymorphism with AIS risk. Significant association was observed in homozygote model of MMP-3-1171-5A/6A gene polymorphism (5A5A versus 6A6A: OR = 1.69, 95% CI = 1.11-2.58, P = 0.02). When stratified into Caucasian and Asian populations, positive association was found in Caucasian population (5A versus 6A: OR = 1.43, 95% CI = 1.11-1.84, P = 0.006; 5A5A versus 6A6A: OR = 1.90, 95% CI = 1.13-3.19, P = 0.015); however, there was no significant association in Asian population. The present study concluded that 5A5A genotype of MMP-3-1171 5A/6A gene polymorphism was associated with AIS, especially in Caucasian population. However, no significant association was detected between IL-6-174-G/C gene polymorphism and AIS.