Association of the MMP-3, MMP-9 and MMP-12 gene polymorphisms with COPD risk: a meta-analysis.

Introduction: Given the evidence that the matrix metalloproteinases (MMPs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a number of case-control studies have attempted to assess the relationship between genetic polymorphisms in MMP genes and COPD risk. However, reliable measures of these results are lacking. Material and methods: We assessed the published evidence for association of the MMP-3, MMP-9 and MMP-12 polymorphisms with COPD risk using meta-analytic techniques. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each study using fixed or random effect models. Results: A total of 23 case-control studies were included in the meta-analysis. No significant association was observed between the MMP-9 rs3918242 polymorphism and COPD risk in the overall populations under the dominant (T/T + C/T vs. C/C: OR = 1.30, 95% CI: 1.00-1.69, p = 0.054) and allele contrast (T allele vs. C allele: OR = 1.22, 95% CI: 0.97-1.53, p = 0.088) models. However, in sub-group analysis the polymorphism rs3918242 was significant in Asians under the dominant model (T/T + C/T vs. C/C: OR = 1.66, 95% CI: 1.02-2.72, p = 0.043). The results for MMP-12 rs2276109 showed an association with COPD only in mixed populations (G/G + A/G vs. A/A: OR = 1.57, 95% CI: 1.10-2.24, p = 0.013; G allele vs. A allele: OR = 1.52, 95% CI: 1.09-2.14, p = 0.015). We did not find any significant association of the MMP-12 rs652438 and MMP-3 rs35068180 polymorphisms with COPD. Conclusions: The findings of this meta-analysis suggest that there is a risk of COPD associated with the MMP-9 rs3918242 and MMP-12 rs2276109 polymorphisms in certain ethnic groups.

Dried fruit intake causally protects against low back pain: A Mendelian randomization study.

Background: Low back pain is the leading cause of years lived with disability worldwide. The aim of this study was to evaluate whether dried fruit intake causally protects against low back pain using two-sample Mendelian randomization (MR). Methods: We obtained summary-level data for dried fruit intake (N = 421,764) from the IEU Open GWAS Project. Forty-one independent genetic variants proxied dried fruit intake. The corresponding data for low back pain were derived from the FinnGen project (13,178 cases and 164,682 controls; discovery data) and the Neale lab (5,423 cases and 355,771 controls; replication data). We conducted univariable and multivariable MR analyses. Results: In the univariable MR analysis, the inverse variance weighted estimate showed that greater dried fruit intake was associated with decreased risk of low back pain [odds ratio (OR) = 0.435, 95% confidence interval (CI): 0.287-0.659, P = 8.657 × 10-5]. Sensitivity analyses using the MR-Egger (OR = 0.078, 95% CI: 0.013-0.479, P = 0.009), maximum likelihood (OR = 0.433, 95% CI: 0.295-0.635, P = 1.801 × 10-5), weighted median (OR = 0.561, 95% CI: 0.325-0.967, P = 0.038) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) (OR = 0.454, 95% CI: 0.302-0.683, P = 4.535 × 10-4) methods showed consistent results. No evidence of directional pleiotropy was identified according to the Egger intercept (intercept P-value = 0.065) or applying the MR-PRESSO method (global test P-value = 0.164). The replication analysis yielded similar results. The multivariable MR revealed that the inverse association between dried fruit intake and low back pain was consistent after adjustment for fresh fruit intake, body mass index, current tobacco smoking, alcohol intake frequency, total body bone mineral density, serum 25-hydroxyvitamin D levels, and vigorous physical activity. Conclusion: This MR study provides evidence to support that dried fruit intake causally protects against low back pain.

Assessment of the Association between Genetic Polymorphisms in the CHI3L1 Gene and Asthma Risk.

BACKGROUND: Chitinase 3-like 1 (CHI3L1) is an important factor involved in the development of asthma. This meta-analysis assessed the association of the CHI3L1 polymorphisms rs4950928, rs10399931, rs883125, rs880633, and rs10399805 with asthma risk. METHODS: The literature searches were conducted in PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure up until September 4, 2021, for relevant studies. Sixteen publications with 18 studies involving 5,005 asthma patients and 9,725 controls were included in this meta-analysis. RESULTS: The meta-analyses showed that among East-Asian subjects, increased asthma risk was associated with CHI3L1 rs4950928 (GG + CG vs. CC: odds ratio [OR] = 1.43, 95% confidence interval [CI]: 1.09-1.88, p = 0.011; GG vs. CG + CC: OR = 1.64, 95% CI: 1.20-2.26, p = 0.002; GG vs. CC: OR = 1.97, 95% CI: 1.41-2.75, p = 0.000; and G vs. C: OR = 1.36, 95% CI: 1.12-1.66, p = 0.002) and rs883125 (G vs. C: OR = 1.42, 95% CI: 1.01-1.99, p = 0.043), whereas CHI3L1 rs10399931 was associated with reduced asthma risk (TT vs. CT + CC: OR = 0.79, 95% CI: 0.64-0.99, p = 0.038; TT vs. CC: OR = 0.77, 95% CI: 0.61-0.98, p = 0.030). In addition, we found an association between CHI3L1 rs4950928 and asthma risk in adult subjects but not children, while CHI3L1 rs883125 was associated with asthma risk in children. CONCLUSION: The CHI3L1 polymorphisms rs4950928, rs10399931, and rs883125 are important genetic factors for asthma among East-Asian subjects.

Identification of SSBP1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches.

OBJECTIVE: Single-stranded DNA-binding protein 1 (SSBP1) plays an important role in DNA repair processes and the maintenance of genomic stability. The aim of this study was to evaluate the expression of SSBP1 and its prognostic value in lung adenocarcinoma (LUAD) using bioinformatics approaches. METHODS: We applied databases including UALCAN, Kaplan-Meier plotter, LinkedOmics, Webgestalt, cBioPortal and TIMER2.0 in this study. RESULTS: We found that SSBP1 expression was up-regulated in LUAD samples and was correlated with clinicopathological features including age, cancer stage, and nodal metastasis status by the UALCAN analysis. Multivariate Cox regression analysis by the Kaplan-Meier plotter showed that high SSBP1 expression was independently correlated with poor overall survival (hazard ratio = 1.63, 95% confidence interval: 1.08-2.46, logrank P = 0.02). The LinkedOmics analysis showed that 5078 genes were positively correlated with SSBP1 expression, whereas 7905 genes were negatively correlated with SSBP1 in LUAD. Functional enrichment analysis using the Webgestalt tool showed that for SSBP1 and the genes positively correlating with it, the significantly enriched biological process was ribosomal large subunit biogenesis, and the significantly enriched pathway was proteasome. According to the cBioPortal database, the frequency of SSBP1 alterations was 1.7% in LUAD patients, and patients with SSBP1 alterations had worse prognosis (logrank P = 4.26e-05) compared with those unaltered for SSBP1. Finally, SSBP1 expression was negatively correlated with B cell infiltration level (Rho = -0.193, P = 1.54e-05) and the expression of B cell biomarkers including CD79A and CD19. CONCLUSION: Our results suggest that SSBP1 may be a prognostic marker for human LUAD.

Development of an Oncogenic Driver Alteration Associated Immune-Related Prognostic Model for Stage I-II Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) needs to be stratified for its heterogeneity. Oncogenic driver alterations such as EGFR mutation, ALK translocation, ROS1 translocation, and BRAF mutation predict response to treatment for LUAD. Since oncogenic driver alterations may modulate immune response in tumor microenvironment that may influence prognosis in LUAD, the effects of EGFR, ALK, ROS1, and BRAF alterations on tumor microenvironment remain unclear. Immune-related prognostic model associated with oncogenic driver alterations is needed. In this study, we performed the Cox-proportional Hazards Analysis based on the L1-penalized (LASSO) Analysis to establish an immune-related prognostic model (IPM) in stage I-II LUAD patients, which was based on 3 immune-related genes (PDE4B, RIPK2, and IFITM1) significantly enriched in patients without EGFR, ALK, ROS1, and BRAF alterations in The Cancer Genome Atlas (TCGA) database. Then, patients were categorized into high-risk and low-risk groups individually according to the IPM defined risk score. The predicting ability of the IPM was validated in GSE31210 and GSE26939 downloaded from the Gene Expression Omnibus (GEO) database. High-risk was significantly associated with lower overall survival (OS) rates in 3 independent stage I-II LUAD cohorts (all P < 0.05). Moreover, the IPM defined risk independently predicted OS for patients in TCGA stage I-II LUAD cohort (P = 0.011). High-risk group had significantly higher proportions of macrophages M1 and activated mast cells but lower proportions of memory B cells, resting CD4 memory T cells and resting mast cells than low-risk group (all P < 0.05). In addition, the high-risk group had a significantly lower expression of CTLA-4, PDCD1, HAVCR2, and TIGIT than the low-risk group (all P < 0.05). In summary, we established a novel IPM that could provide new biomarkers for risk stratification of stage I-II LUAD patients.

Single nucleotide polymorphisms of IL-13 and CD14 genes in allergic rhinitis: a meta-analysis.

PURPOSE: The aim of this study was to conduct a meta-analysis for single nucleotide polymorphisms (SNPs) in interleukin-13 (IL-13) and cluster of differentiation 14 (CD14) genes and the risk for allergic rhinitis (AR). METHODS: We screened studies identified through seven databases including Pubmed, Medline, Web of Science, Embase, China Biology Medicine disc, Wanfang, and China Academic Journal Network Publishing Database. The odds ratios (ORs) and 95% confidence intervals (CIs) were determined to assess the association under allelic, dominant and recessive models. RESULTS: Twelve studies with a total of 8547 participants (3223 cases and 5324 controls) investigated IL-13 SNP rs20541, five studies combining 4580 participants (1411 cases and 3169 controls) examined IL-13 SNP rs1800925, and nine studies with 2301 participants (1174 cases and 1127 controls) assessed CD14 SNP rs2569190. We found that the A allele of IL-13 SNP rs20541 was associated with an increased risk of AR (OR 1.19, 95% CI 1.11-1.28, P < 0.001). Stratifying studies by ethnic group produced significant results in Asians (OR 1.21, 95% CI 1.11-1.32, P < 0.001), but not in Caucasians (OR 1.14, 95% CI 1.00-1.30, P = 0.051). No association of IL-13 SNP rs1800925 and CD14 SNP rs2569190 with AR risk was found in either Asians or Caucasians (P > 0.05). CONCLUSION: Our findings suggest that IL-13 SNP rs20541 is significantly associated with AR risk in Asians but not in Caucasians. However, the accumulating evidence does not support an association of IL-13 SNP rs1800925 and CD14 SNP rs2569190 with AR risk.

Association between the TGF-ß1 polymorphisms and chronic obstructive pulmonary disease: a meta-analysis.

It has been hypothesized that polymorphisms in the transforming growth factor-ß1 (TGF-ß1) gene on chromosome 19 modify the risk for chronic obstructive pulmonary disease (COPD). However, results from previous studies are contradictory. We therefore conducted a meta-analysis of published case-control studies on the association between five common TGF-ß1 polymorphisms (rs1982073, rs1800469, rs2241712, rs6957, and rs2241718) and COPD risk. Data sources were Pubmed, Scopus, ISI Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Twelve studies including 6749 participants were reviewed and analyzed. For the TGF-ß1 polymorphism rs1982073, the results indicted that the C allele was associated with decreased risk of COPD in Caucasians (odds ratio (OR) =0.79, 95% confidence interval (CI): 0.64-0.99, P=0.038) but not in Asians (OR =0.95, 95% CI: 0.71-1.28, P=0.741). No associations with COPD were identified for other polymorphisms evaluated in the present study including rs1800469 (T allele compared with C allele, OR =0.89, 95% CI: 0.77-1.02, P=0.099), rs2241712 (A allele compared with G allele, OR =1.03, 95% CI: 0.89-1.20, P=0.666), rs6957 (A allele compared with G allele, OR =1.14, 95% CI: 0.95-1.36, P=0.160), and rs2241718 (C allele compared with T allele, OR =0.95, 95% CI: 0.79-1.14, P=0.571). In conclusion, this meta-analysis showed that the C allele of rs1982073 was protective against COPD in Caucasians but not in Asians, whereas there was no association of rs1800469, rs2241712, rs6957, and rs2241718 with COPD.

Association of the IL-13 polymorphisms rs1800925 and rs20541 with chronic obstructive pulmonary disease risk: An updated meta-analysis.

The aim of this study was to investigate if 2 common single nucleotide polymorphisms (SNPs) in the interleukin-13 (IL-13) gene, rs1800925 and rs20541 are associated with chronic obstructive pulmonary disease (COPD) risk.Case-control association studies were retrieved systematically from PubMed, Scopus, ISI Web of Science, China National Knowledge Infrastructure, and Wanfang databases using standardized subject terms.Eleven studies including 3077 participants (1896 cases and 1181 controls) were analyzed. Evidence for a positive association between the T allele of the IL-13 SNP rs1800925 and COPD risk was found in the overall population (odds ratio [OR] = 1.57, 95% confidence interval [95% CI]: 1.21-2.04, Pz = .001). In subgroup analysis according to ethnicity, the T allele of rs1800925 was associated with an increased risk of COPD in Asians (OR = 1.88, 95% CI: 1.23-2.87, Pz = .004) and Caucasians (OR = 1.30, 95% CI: 1.01-1.67, Pz = .041), respectively. For rs20541, the results suggested an association between rs20541 and COPD risk in Caucasians under the recessive model (OR = 2.79, 95% CI: 1.13-6.92, Pz = .026), whereas this SNP was not associated with COPD in Asians.This meta-analysis suggests that the T allele of rs1800925 is associated with the increased risk of COPD in both Asians and Caucasians, whereas rs20541 is associated with the risk of COPD in Caucasians but not in Asians.

Association Between Paraoxonase 2 Ser311Cys Polymorphism and Coronary Heart Disease Risk: A Meta-Analysis.

BACKGROUND The relationship between coronary heart disease (CHD) and the paraoxonase 2 (PON2) Ser311Cys polymorphism has received much attention. We conducted a meta-analysis on the results from published case-control studies examining this relation. MATERIAL AND METHODS A literature search was performed using PubMed and ISI Web of Knowledge databases until October 2015. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using Stata version 11.0 software. Data were pooled using the random-effects model. RESULTS Nine studies were eligible for statistical analysis and included a total of 5278 participants. The results did not support an association between the Ser311Cys polymorphism and CHD in the overall populations (Asians, Caucasians, and a Hispanic mixed population) under dominant (OR 1.07; 95% CI 0.91-1.28; Pz=0.413), recessive (OR 1.19; 95% CI 0.72-1.95; Pz=0.500), homozygote (OR 1.20; 95% CI 0.71-2.03; Pz=0.489), and allelic comparison (OR 1.08; 95% CI 0.91-1.28; Pz=0.390) models. However, in subgroup analysis according to ethnicity, we found that the Ser311Cys polymorphism was associated with CHD risk in Caucasians under recessive (OR 2.08; 95% CI 1.30-3.34; Pz=0.002) and homozygote (OR 2.16; 95% CI 1.33-3.50; Pz=0.002) models. Subgroup analysis indicated no significant association of this polymorphism with CHD in either Asian or Hispanic populations. CONCLUSIONS The PON2 Ser311Cys polymorphism is associated with CHD risk in Caucasians, but there is no association between this polymorphism and CHD in Asians or Hispanic populations.

Association between the MYO9B polymorphisms and celiac disease risk: a meta-analysis.

BACKGROUND: There is no consensus regarding the association between polymorphisms in the myosin IXB (MYO9B) gene and celiac disease (CD) risk. In this study, we performed a meta-analysis to evaluate genetic variants in MYO9B with CD. METHODS: Four MYO9B polymorphisms (rs1545620, rs1457092, rs2305767 and rs2305764) were assessed. A literature search was conducted using PubMed, Scopus, and Web of Science databases until June 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association under dominant, recessive, homozygote and allelic comparison models. RESULTS: Seven case-control studies with a total of 1965 CD patients and 4894 controls were included in this meta-analysis. The results showed that rs1545620 was associated with CD risk in Europeans in dominant (OR=1.31, 95% CI: 1.10-1.58, Pz =0.003), recessive (OR=1.36, 95% CI: 1.08-1.72, Pz =0.009), homozygote (OR=1.55, 95% CI: 1.20-2.01, Pz =0.001), and allelic comparison models (OR=1.24, 95% CI: 1.10-1.40, Pz =0.001), whereas in a Latin American group there were significant associations of CD with rs1457092 in dominant (OR=15.30, 95% CI: 3.51-66.67, Pz <0.001), homozygote (OR=16.55, 95% CI: 3.62-75.65, Pz <0.001), and allelic comparison models (OR=1.95, 95% CI: 1.31-2.91, Pz =0.001), and rs2305767 in dominant (OR=5.35, 95% CI: 2.42-11.86, Pz <0.001) and allelic comparison models (OR=1.65, 95% CI: 1.11-2.45, Pz =0.013). There was no association between rs2305764 and CD risk in either Europeans or the Latin American group. CONCLUSION: rs1545620 is associated with CD risk in Europeans, whereas rs1457092 and rs2305767 are associated with CD risk in a Latin American group.

Lack of Association Between the IL1B (-511 and +3954), IL1RN VNTR Polymorphisms and Tuberculosis Risk: A Meta-analysis.

BACKGROUND: Several recent studies have provided evidence that polymorphisms in the interleukin-1 (IL1) gene are implicated in tuberculosis (TB). However, results of different studies are inconsistent. The aim of this study was to perform a meta-analysis investigating the association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk. METHODS: A systematic review of the English literature was conducted by searching Pubmed, Scopus, and ISI Web of Knowledge databases for relevant studies. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated using fixed effects models. Between-study heterogeneity and publication bias were also evaluated. RESULTS: Nine case-control studies including 3327 participants were reviewed and analyzed. Our results did not indicate any association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk in the overall populations. The pooled OR of the IL1B -511 polymorphism was 1.09 (95 % CI 0.87-1.36) for the dominant model, 1.11 (0.89-1.38) for the recessive model, 1.15 (0.87-1.50) for the homozygote model, and 1.07 (0.94-1.23) for the allelic comparison model. ORs for the IL1B +3954 and IL1RN VNTR polymorphisms were similar. In subgroup analysis stratified by ethnicity, the results revealed no association between these polymorphisms and TB risk in black people, Asians, and Caucasians, respectively. We did not identify significant between-study heterogeneity across all studies, and there was no evidence of publication bias. CONCLUSIONS: Our results indicate there is a lack of association between the IL1B (-511 and +3954), IL1RN VNTR polymorphisms and TB risk.

Association between the IL1B, IL1RN polymorphisms and COPD risk: a meta-analysis.

The interleukin-1 (IL-1) gene polymorphisms have been implicated in chronic obstructive pulmonary disease (COPD) risk, but results are controversial. We aimed to conduct a meta-analysis to address this issue. Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association. The meta-analysis revealed no association between the IL1B (-511), (-31), (+3954) polymorphisms and COPD risk. However, stratification by ethnicity indicated that the T allele carriers of the IL1B (-511) polymorphism and the C allele carriers of the IL1B (-31) variant were associated with an increased risk for developing COPD in East Asians (OR = 1.61, 95% CI: 1.13-2.31, Pz = 0.009 and OR = 1.55, 95% CI: 1.14-2.11, Pz = 0.006, respectively). The meta-analysis revealed a significant association between the IL1RN (VNTR) polymorphism and COPD risk in all study subjects and East Asians under homozygote model (22 vs. LL: OR = 3.16, 95% CI: 1.23-8.13, Pz = 0.017 and OR = 3.20, 95% CI: 1.13-9.12, Pz = 0.029, respectively). Our meta-analysis suggests that the IL1B (-511), (-31) and IL1RN (VNTR) polymorphisms are associated with COPD risk in East Asians. There is no association between the IL1B (+3954) polymorphism and COPD risk. Further studies should be performed in other ethnic groups besides East Asians.

The regulated upon activation normal T-cell expressed and secreted (RANTES) -28C/G and -403G/A polymorphisms and asthma risk: a meta-analysis.

BACKGROUND AND OBJECTIVES: Genetic studies have revealed that the regulated upon activation normal T-cell expressed and secreted (RANTES) -28C/G and -403G/A polymorphisms are associated with asthma risk, but contradictory findings have also been reported. Therefore, we undertook a meta-analysis on this topic. METHODS: The PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases were used to identify relevant studies published in the medical literature from 1990 to March 26, 2014. Nine studies (containing 2,103 cases and 2,876 controls) investigated the -28C/G polymorphism, and 11 studies (including 2,015 cases and 1,909 controls) assessed the -403G/A polymorphism. RESULTS: The pooled results demonstrated that the -28C/G polymorphism was not associated with asthma risk in the overall populations (Caucasians, Asians, and a mixed population). However, in subgroup analysis according to age, the -28G allele was associated with an increased risk of asthma in children (odds ratio [OR] 1.27, 95 % confidence interval [CI] 1.03-1.57, P value for heterogeneity [P het] = 0.163, P value for the overall effect [P z] = 0.028). When we further stratified the studies performed in children on the basis of ethnicity, we found that the -28G allele was associated with an increased risk of asthma in Asian children (OR 1.28, 95 % CI 1.02-1.62, P het = 0.127, P z = 0.035), but not in Caucasian children (OR 1.20, 95 % CI 0.68-2.12, P het = 0.137, P z = 0.530). In subgroup analysis by asthma phenotype, no association between either atopic or non-atopic asthma and the -28C/G polymorphism was identified. For the -403G/A polymorphism, meta-analysis showed no association with asthma risk in the overall populations (Caucasians, Asians, and black people). In subgroup analyses by age, ethnicity, and asthma phenotype, we still did not find any association between the -403G/A polymorphism and asthma. CONCLUSION: Current findings suggest an association between the -28G allele and asthma risk in Asian children but not in Caucasian children.

Lack of association between the IL-13 C-1112T, G2044A polymorphisms and Graves' disease risk: evidence from a meta-analysis.

BACKGROUND: Previous studies have provided conflicting evidence implicating the IL-13 C-1112T and G2044A polymorphisms in Graves' disease (GD) risk. We undertook a meta-analysis to address this issue. METHODS: The Medline, Pubmed and Web of Science databases were searched for published case-control studies investigating the relation of the IL-13 C-1112T and G2044A polymorphisms with GD risk. Data were extracted using standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Available data did not suggest an association between any of the two IL-13 polymorphisms and GD risk. For the C-1112T polymorphism, the combined OR was 0.96 (95% CI: 0.77-1.19) for dominant model (TT+CT vs CC), 0.97 (95% CI: 0.69-1.38) for recessive model (TT vs CT+CC), and 0.97 (95% CI: 0.68-1.39) for homozygote model (TT vs CC). ORs for the G2044A polymorphism were similar. In subgroup analyses stratified by ethnicity, we also did not find associations between these two variants and GD risk in Asians or Caucasians. Sensitivity analyses by excluding each of the involved study in turn did not change the pooled results. CONCLUSION: The IL-13 C-1112T and G2044A polymorphisms are not associated with GD risk.

Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves' disease risk: a meta-analysis of 11 case-control studies.

BACKGROUND: Data on the association between the interleukin-1 (IL-1) gene polymorphisms and Graves' disease (GD) risk were conflicting. A meta-analysis was undertaken to assess this association. METHODS: We searched for case-control studies investigating the association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk. We extracted data using standardized forms and calculated odds ratios (OR) with 95% confidence intervals (CI). RESULTS: A total of 11 case-control studies were included in this meta-analysis. Available data indicated that the IL1B (-511) polymorphism was associated with GD risk in the overall populations (Caucasians and Asians) in homozygote model (TT vs. CC, OR = 0.86, 95% CI: 0.76-0.97, Pz  = 0.015), but not in dominant and recessive models (TT+TC vs. CC: OR = 0.95, 95% CI: 0.81-1.12, Pz  =  0.553 and TT vs. TC+CC: OR = 0.82, 95% CI: 0.60-1.12, Pz  =  0.205, respectively). No association between the IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk was found in the overall populations in any of the genetic models. In subgroup analyses according to ethnicity, the IL1B (-511) polymorphism was associated with GD risk in Asians in recessive and homozygote models (TT vs. TC+CC: OR =  0.68, 95% CI: 0.55-0.84, Pz < 0.001 and TT vs. CC: OR = 0.81, 95% CI: 0.70-0.93, Pz  =  0.003, respectively), but not in dominant model (TT+TC vs. CC: OR =  0.92, 95% CI: 0.77-1.11, Pz  =  0.389). No association between the IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk was indicated in Asians, and we found no association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk in Caucasians in any of the genetic models. CONCLUSION: The IL1B (-511) polymorphism, but not the IL1B (+3954) and IL1RN (VNTR) polymorphisms was associated with GD risk in Asians. There was no association between these polymorphisms and GD risk in Caucasians.

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

AIMS: Data on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic. METHODS: We 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. RESULTS: Six 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, P(z)=0.030). CONCLUSION: The 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.

Association of interleukin-1 gene polymorphisms with multiple sclerosis: a meta-analysis.

BACKGROUND: Dysregulated levels of interleukin-1 (IL-1) were observed in patients with multiple sclerosis (MS). Previous studies have provided conflicting evidence implicating the IL-1 gene polymorphisms in MS risk. METHODS: A meta-analysis of 16 case-control studies involving 3,482 cases and 3,528 controls was conducted to evaluate this association. RESULTS: No association was found between the IL-1α -889 (rs1800587), IL-1α +4,845 (rs17561), IL-1ß -511 (rs16944), IL-1ß +3,953 (rs1143634), IL-1ra variable number tandem repeat (VNTR) polymorphisms and MS risk. However, in subgroup analyses for the IL-1ra VNTR polymorphism, we found that individuals carrying the 2 allele had a 32 % increased risk for bout-onset MS (relapsing remitting and secondary progressive MS) when compared to the LL homozygotes (OR = 1.32, 95 % CI = 1.06-1.66, P (z) = 0.014). CONCLUSION: Common variants in the IL-1 region are not associated with MS risk but our data suggest that the IL-1ra VNTR polymorphism might be associated with bout-onset MS subtype.

Association between tumor necrosis factor-α-308G/A polymorphism and obstructive sleep apnea: a meta-analysis.

BACKGROUND AND OBJECTIVE: The tumor necrosis factor (TNF)-α-308G/A polymorphism has been implicated in susceptibility to obstructive sleep apnea (OSA). However, results from previous studies are inconsistent. A systematic review and meta-analysis of the published studies was performed to investigate this association. METHOD: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Weipu databases for published studies evaluating the association between -308G/A polymorphism and OSA. Data were extracted using standardized forms and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Four case-control studies involving a total of 419 cases and 460 controls were included in the meta-analysis. Combined data indicated that individuals carrying the -308A allele had a 65% increased risk of developing OSA when compared with the GG homozygotes (OR=1.65, 95% CI=1.02-2.68, p=0.04). In adults, the risk was even higher, elevated by 100% (OR=2.00, 95% CI=1.26-3.18, p=0.003). CONCLUSION: The TNF-α-308G/A polymorphism contributes to the risk of OSA, especially in adults.