Previous studies that evaluated the association between a disintegrin and metalloprotease 12 (ADAM12) gene polymorphisms and knee osteoarthritis (KOA) have given controversial and indefinite results. Therefore, we performed a meta-analysis to confirm this correlation. We searched the PubMed, Embase, and SinoMed databases for all papers published up to April 11, 2017. Overall, five different studies, totaling 2,353 cases and 3,668 controls, were retrieved on the basis of the search criteria for KOA susceptibility related to four polymorphisms (rs3740199, rs1278279, rs1871054, and rs1044122) in the ADAM12 gene. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using Egger's and Begg's tests. The rs3740199 G/C polymorphism was found to be associated with increased KOA risk in men (e.g., CG versus GG: OR = 1.44, 95% CI = 1.02–2.04, P = 0.040), but not in the overall analysis and in analyses of other subgroups. Significantly increased associations were also found for the rs1871054 polymorphism (e.g., C versus T allele: OR = 1.85, 95% CI = 1.49–2.30, P < 0.001). However, there were no associations for the rs1278279 and rs1044122 polymorphisms. Furthermore, no obvious evidence of publication bias was detected. Our study indicated that the rs1871054 polymorphism of ADAM12 was significantly associated with increased KOA risk.
Numerous studies have uncovered the association of Interleukin-10 (IL-10) gene rs1800896 polymorphism with the risk of prostate cancer (PCa); however, their conclusions were inconsistent. Therefore, we conducted this meta-analysis to evaluate the role of IL-10 rs1800896 polymorphism in the risk of PCa. 16 eligible studies in 15 articles involving 6,301 cases and 6,510 controls were identified by researching PubMed, Google, CNKI, and EMBASE up to April 1, 2017. Our results revealed that IL-10 rs1800896 polymorphism was associated with the decreased risk of PCa under the homozygous model. Subgroup analysis by ethnicity revealed that rs1800896 polymorphism decreased the risk of PCa among Caucasians. In conclusion, IL-10 gene rs1800896 polymorphism is associated with the decreased risk of PCa. Larger studies with more diverse ethnic populations are needed to confirm these results.
A single nucleotide polymorphism (SNP) of the protein kinase catalytic subunit alpha-1 gene (PRKAA1) that confers susceptibility to gastric cancer (GC) was identified by genome-wide association in several case-control studies. However, the results remained controversial and ambiguous. Therefore, we performed a larger meta-analysis to confirm this association. We searched the PubMed, Embase, WanFang, and CNKI databases, without any restriction on language, covering all papers published until Feb 22, 2017. Overall, 14 case-control studies with 14,485 cases and 14,792 controls were retrieved based on the search criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the strength of the association. Publication bias was assessed by Egger’s and Begg’s tests. We found that the PRKAA1 rs13361707 C/T polymorphism had no association with GC risk in any of the pooled genetic models (for example, the T-allele vs. C-allele allelic contrast model yielded the following estimates: OR = 0.87, 95% CI = 0.73–1.05, Pheterogeneity = 0.000). Furthermore, in analyses stratified by either source of control or geographical origin of subjects, a statistically significant inverse relationship was detected between PRKAA1 rs13361707 C/T polymorphism and GC risk. No obvious evidence of publication bias was detected in the pooled meta-analysis. Furthermore, we observed that individuals carrying T-allele (TT or TC) genotypes had a lower expression of PRKAA1. Our present study indicated that PRKAA1 rs13361707 C/T was not significantly associated with GC risk, despite few positive results in the subgroups.
Controversial results concerning the association between a polymorphism rs6822844 in the interleukin (IL) 21 (IL-21) gene and rheumatoid arthritis (RA) have existed. A meta-analysis to confirm above relationships is necessary to be performed immediately. We conducted a search in the PubMed database, covering all papers published up to 20 October 2018. Overall, six case–control studies with 3244 cases and 3431 healthy controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed with both Egger’s and Begg’s tests. After calculation, we found that IL-21 rs6822844 polymorphism could decrease RA risk in overall genetic models (allelic contrast: OR = 0.77, 95% CI = 0.62–0.97, P=0.024; TG versus GG: OR = 0.68, 95% CI = 0.50–0.92, P=0.013, and dominant genetic model: OR = 0.72, 95% CI = 0.55–0.94, P=0.016). Similarly, stratified analysis by race, source of control, significantly decreased association was found in Asians, Caucasians and hospital-based (HB) control source. Finally, in the subgroup analysis of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status, poorly decreased relationship was detected between IL-21 rs6822844 polymorphism and RF negative and ACPA positive RA risk, respectively. No obvious evidence of publication bias was detected in overall analysis. In summary, our study indicated that IL-21 rs6822844 polymorphism was significantly associated with decreased RA susceptibility.
Methionine synthase (METH, i.e., MTR) is a key enzyme in the folate pathway, which plays a critical role in the synthesis, repair, and methylation of DNA. The association between METH gene polymorphisms and prostate cancer susceptibility remains ambiguous. Thus, we performed an updated meta-analysis of METH single-nucleotide polymorphism rs1805087 involving 12 independent case-control studies comprising 9986 prostate cancer patients and 40134 controls. The odds ratio and 95% confidence intervals were applied to evaluate the relation of this single-nucleotide polymorphism with prostate cancer. Statistical analysis was performed in STATA 11.0. A significant association was found between rs1805087 and increased prostate cancer risk, overall and with Hardy–Weinberg equilibrium. In subgroup analyses (based on ethnicity, source of control, genotyping methods, or publication status), similar associations were observed (e.g., genotype GA vs. AA: odds ratio 1.19, 95% confidence interval 1.01–1.40 among whites; G allele vs. A allele: odds ratio 1.14, 95% confidence interval 1.02–1.28 among hospital-based controls). Thus, the common polymorphism (rs1805087) of METH may be associated with increased prostate cancer risk. Further studies with a larger sample size and detailed gene–environment interactions should be conducted to identify the role of METH polymorphisms in prostate cancer susceptibility.
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