Association of Interleukin 10 (IL-10) Gene Polymorphism (819T > C) with Susceptibility to Acute Myeloid Leukemia: A Meta-Analysis

Background: Studies reported an association between interleukin (IL)-10 -819T>C polymorphism and the risk of developing Acute myeloid leukemia (AML), however due to inconsistency among these results, relationship between IL-10 -819T>C polymorphism and AML remained unclear. We herein performed this meta-analysis to investigate the association of IL-10 -819T >C polymorphism with the risk of AML. Methods: A systematic search through PubMed, Embase, Scopus, Cochrane Library and OpenGrey was performed from inception to Jan 2021. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was assessed using the Cochran Q test and the I2 statistic. A total of 404 AML cases and 635 healthy controls were included in our meta-analysis. Results: Our results indicated no statically significant association between IL-10 -819T>C polymorphism and the risk of developing AML; dominant model (OR=0.87, 95% CI=0.42–1.81); recessive model (OR=1.17, 95% CI = 0.43–3.16); allelic model (OR=1.00, 95% CI=0.54–1.88); CC vs. TT (OR=1.00,95% CI=0.30–3.36); and TC vs. TT (OR=0.80, 95%CI =0.46–1.37). Conclusion: IL-10 -819T > C polymorphism is not associated with the risk of AML. However further studies focusing on other parameters such as sex, gene-gene interactions and environmental factors are required to reveal the true association of IL-10 -819T > C polymorphism with AML.

Genetic Polymorphism rs6505162 in MicroRNA-423 May Not Be Associated with Susceptibility of Breast Cancer: A Systematic Review and Meta-Analysis

Background. MicroRNA-423 (miR-423) rs6505162 polymorphism is found to be associated with breast cancer (BC) risk. However, the results were inconsistent. This study meta-analyzed the literature on possible association between rs6505162 polymorphism and BC risk. Methods. PubMed, Embase, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association between rs6505162 polymorphism and BC. Results. None of the five genetic models suggested a significant association between rs6505162 polymorphism and BC risk: allelic model, OR 1.02, 95% CI 0.18–1.28, P = 0.85 ; recessive model, OR 0.99, 95% CI 0.72–1.38, P = 0.97 ; dominant model, OR 0.93, 95% CI 0.72–1.21, P = 0.60 ; homozygous model, OR 1.04, 95% CI 0.66–1.65, P = 0.87 ; and heterozygous model, OR 1.07, 95% CI 0.90–1.28, P = 0.45 . Similar results were obtained in subgroup analyses of Asian, Chinese, and Caucasian patients. Conclusion. The available evidence suggests no significant association between rs6505162 polymorphism and BC risk. These conclusions should be verified in large, well-designed studies.

Is There a Relation between 677C>T Polymorphism in the MTHFR Gene and the Susceptibility to Epilepsy in Young Patients? A Meta-Analysis

Background: Numerous data show a role for genetic polymorphisms in the development of epilepsy. Previously, the TT genotype of the MTHFR 677C>T polymorphism was found to be associated with a decreased leucocyte DNA methylation status. Polymorphisms in the MTHFR gene could modify the pharmacodynamics of many drugs. This meta-analysis aimed to assess the relationship between MTHFR 677C>T polymorphism and susceptibility to epilepsy in young patients. Methods: Available databases (PubMed, Embase, Google Scholar, SciELO, and Medline) were searched using specific keywords. Eight studies, published between 1999 and 2019, with 1678 young patients with epilepsy and 1784 controls, met the inclusion criteria. Apart from the total groups, additional analyses in age subgroups (i.e., young adults and children) were conducted. Statistical analyses were conducted using the RevMan 5.4 and MedCalc software. The pooled odds ratio (OR) was estimated with a random- or fixed-effects model depending on the heterogeneity. Analyses were performed for five genetic models, i.e., dominant (CT + TT vs. CC), recessive (TT vs. CC + CT), additive (TT vs. CC), heterozygous (CT vs. CC), and allelic (T vs. C). The publication bias was assessed with the use of Egger’s and Begg’s tests. Results: Both the MTHFR TT genotype (in the additive model) and the T allele (in the allelic model) significantly increased the risk of epilepsy when the total groups were compared (OR = 1.44, p = 0.002, and OR = 1.183, p = 0.001, respectively). The sensitivity analysis for these models indicated the stability of the results. Similarly, significant results were obtained among young adults for all the genetic models (dominant model: OR = 1.28, p = 0.002; recessive model: OR = 1.48, p = 0.003; additive model: OR = 1.63, p < 0.001; heterozygous model: OR = 1.21, p = 0.028; and allelic model: OR = 1.256, p < 0.001). Those results were also stable and reliable. In the group of children, no relation between 677C>T polymorphism and epilepsy was observed; however, the analysis was based only on three studies, and one study also comprised young adults. No publication bias was demonstrated. Conclusions: The meta-analysis revealed that the carrier state for the T allele as well as the TT genotype of the MTHFR 677C>T polymorphism increases the risk of epilepsy in young adults but not in children.

Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Objective This meta-analysis was conducted to investigate the relationship between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis (RA) susceptibility. Methods Eligible studies were retrieved from PubMed, Embase, and Web of Science. The fixed- or random-effects model was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) on the basis of heterogeneity. Results Overall, 11 studies containing 4019 RA patients and 4137 controls were included in this meta-analysis. The results suggested a significant association between the IL-17A rs2275913 polymorphism and RA susceptibility in the overall population (allelic model A vs. G: OR = 0.89, 95%CI: 0.83–0.95; heterozygote model GA vs. GG: OR = 0.87, 95%CI: 0.78–0.96; homozygote model AA vs. GG: OR = 0.82, 95%CI: 0.71–0.96; dominant model GA + AA vs. GG: OR = 0.86, 95%CI: 0.78–0.94). In the subgroup analyses, the IL-17A rs2275913 polymorphism was significantly associated with RA risk in Europeans (allelic model A vs. G: OR = 0.87, 95%CI: 0.78–0.97; heterozygote model GA vs. GG: OR = 0.79, 95%CI: 0.68–0.93; dominant model GA + AA vs. GG: OR = 0.79, 95%CI: 0.68–0.92), but not in Africans or Americans. Conclusion This study suggests that the IL-17A rs2275913 polymorphism is significantly associated with RA susceptibility in Europeans. INPLASY registration number: INPLASY202170056.

The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis

Background The gene NKX2-5 is a key transcription factor that plays an essential role in normal cardiac development. Although some recent studies have studied the role of polymorphisms in the NKX2-5 gene in congenital heart diseases (CHDs), the results were not consistent and remained uncertain. Therefore, we conduct a review of literature and investigate the association of genetic polymorphisms with CHDs. Results We selected seventeen studies regarding the association of NKX2-5 gene rs2277923 polymorphism with CHDs. Overall, in all the tested genetic models, the 63A > G polymorphism was not significantly associated with increased congenital heart defects risk. We used pooled odds ratios (OR) to calculate the association of CHDs with rs2277923 including allelic model: OR 1.00, 95% CI 0.82–1.21; homozygote model: OR 0.95, 95%CI 0.68–1.33, recessive model: OR 0.89 CI 0.70–1.13, heterozygote model: OR: 1.09, 95%CI 0.87–1.37, dominant model: OR 1.08 CI 0.82–1.42 and overdominant model: OR 1.17 CI 1.01–1.35. In addition, our analysis suggests that no publication bias exists in this meta-analysis. Conclusions Our findings suggested that 63A > G polymorphism in the NKX2-5 gene was not significantly associated with congenital heart defects. However, in the future, more studies with increased sample size are required that may provide us more definite conclusions.

Correlation between hypoxia-inducible factor-1α C1772T/G1790A polymorphisms and head and neck cancer risk: a meta-analysis

Objective This meta-analysis was implemented to evaluate the association between hypoxia-inducible factor-1α (HIF-1α) C1772T/G1790A polymorphisms and susceptibility to head and neck cancer (HNC). Material and methods This meta-analysis has been registered on PROSPERO platform (CRD42021257309). The PubMed, Embase and Web of Science databases were searched to retrieve eligible published papers. STATA software was used to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the correlation strength. Results Our results demonstrated that the HIF-1α C1772T polymorphism was significantly related to an increased HNC risk (OR = 2.27, 95% CI = 1.17–4.42 for the homozygous model; OR = 11.53, 95% CI = 1.11–120.4 for the recessive model), especially in Caucasians (OR = 2.16, 95% CI = 1.09–4.27 for the homozygous model; OR = 2.28, 95% CI = 1.15–5.51 for the recessive model). Similarly, a remarkable correlation was discovered between the G1790A polymorphism and HNC risk (OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 58.05, 95% CI = 1.70–1985.77 for the recessive model). Moreover, in the subgroup analysis by source of controls, a statistically significant correlation was discovered in the population-based (PB) subgroup (OR = 9.43, 95% CI = 1.20–73.9 for allelic model; OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 3.22, 95% CI = 1.28–8.08 for the heterozygous model; OR = 7.83, 95% CI = 1.48–41.37 for the dominant model; OR = 58.05, 95% CI = 1.70–1985.8 for the recessive model) but not in the hospital-based (HB) subgroup. Conclusion Our study found that both HIF-1α C1772T and G1790A polymorphisms might be a higher risk of HNC, especially in the Caucasian group with the C1772T polymorphism.

Association of Interleukin-10 Polymorphism (rs1800896, rs1800871, and rs1800872) with Breast Cancer Risk: an Updated Meta-Analysis Based on Different Ethnic Groups

Background: There have been various publications stating that IL-10 gene polymorphism is connected with the risk of breast cancer.This study was to further evaluate the association between IL-10 gene polymorphism and breast cancer (BC).Methods: Articles from PubMed, Web of Knowledge, Embase, CNKI databases, China biomedical (CBM), and Google Scholar before March 29, 2020. The data was analyzed by Revman5.3 and Stata 12.0 software, and the strength of the association was identified using the odds ratio (OR) and the corresponding 95% confidence interval (CI).Results: A total of 23 studies (7250 cancer cases and 7675 case-free controls) were eligible for the mate-analysis. The results show that IL-10 gene polymorphisms has no association with BC risk in any genetic model of the general population. However, there is significantly correlated with BC risk based on subgroup analysis by ethnicity: rs1800896 polymorphism are significantly associated with the risk of BC in Asian population based on the four models (G vs. A: OR= 0.78, 95% CI=0.65-0.95, P= 0.01; GG vs. AA: OR=0.51, 95% CI=0.31-0.84, P=0.007; GA vs. AA: OR=0.6, 95% CI=0.44-0.81, P=0.0009; GG+GA vs. AA: OR=0.6, 95% CI=0.45-0.81, P= 0.0007); rs1800871 polymorphism has association with BC risk in Caucasian population based on the Heterozygous model (CT vs. TT: OR=1.8, 95% CI =1.03-3.13, P=0.04). rs1800872 homozygous model was associated with the BC risk in Asians(AA vs CC: OR=0.74, 95%CI =0.55-0.99, P =0.04), and allelic model was associated with BC risk among Asians (A vs C: OR= 0.85, 95% CI =0.74-0.98, P= 0.03) and among Caucasians (A vs C: OR= 0.65, 95% CI 0.43-0.98, P =0.04). Conclusion: IL-10 gene polymorphism rs1800896 and rs1800872 significantly increased the risk of breast cancer in Asians, while rs1800871 was associated with the risk of breast cancer in Caucasians. Therefore, vulnerable individuals can be identified by genotypic characteristics, and the diseases can be prevented through interventions aimed at high-risk groups.

The CYP19A1 (TTTA)n Repeat Polymorphism May Affect the Prostate Cancer Risk: Evidence from a Meta-Analysis

Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, the results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting. This meta-analysis aimed to systematically evaluate the associations between the CYP19A1 Arg264Cys polymorphism and the (TTTA)n repeat polymorphism and PCa. Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of the association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we sequentially took the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95% CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population or in the Caucasian or Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR = 1.34, 95% CI = 1.14–1.58, p = .001) and in the subgroup with population-based (PB) controls (OR = 1.41, 95% CI = 1.13–1.74, p = .002) as well as in the subgroup using capillary electrophoresis to identify this polymorphism (OR = 1.34, 95% CI = 1.09–1.65, p = .006).The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not the Arg264Cys polymorphism, may affect PCa risk.

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

Background: Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting.This meta-analysis aimed to systematically evaluate the association between the CYP19A1 Arg264Cys polymorphism and (TTTA)n repeat polymorphism and PCa.Methods: Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratio (OR) and 95% confidence interval (95% CI) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we took sequentially the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95%CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Results: Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population and in the Caucasian and Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR=1.34, 95% CI=1.14–1.58, P=0.001) and in the subgroup with population-based (PB) controls (OR=1.41, 95% CI=1.13–1.74, P=0.002) as well as in the subgroup of studies using capillary electrophoresis to identify this polymorphism (OR=1.34, 95%CI=1.09-1.65, P=0.006). Conclusions: The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism may affect PCa risk.

Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

Background: The relation between methylenetetrahydrofolate reductase)MTHFR( polymorphisms and the risk of developing Chronic lymphocytic leukemia (CLL) is not still clear, while there are reports about the association of MTHFR C677T and A1298C polymorphisms with developing CLL, there are other reports that rolled out the association of MTHFR polymorphisms with developing CLL. Therefore herein we carried out this meta-analysis to clear the association of MTHFR polymorphisms with the risk of CLL Methods: A comprehensive search was performed through PubMed, Scopus and Embase from inception to Aug 2020. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was evaluated using the Cochran Q test and the I2 statistic. Results: Totals of 1290 cases and 1887 controls for the C677T polymorphism and 1117 cases and 1256 controls for the A1298C polymorphism were included in our analysis. Analyzing the MTHFR C677T and A1298C polymorphisms genotypes showed an association between MTHFR polymorphism at A1298C under Allelic model and the risk of CLL (OR = 1.12, 95% CI = 1.01–1.25), however there was no association between MTHFR polymorphism at MTHFR C677T and risk of CLL. Conclusion: The risk of developing CLL might be associated with MTHFR polymorphism at A1298C under allelic model and not associated with MTHFR polymorphisms at C677T, However, further studies considering other factors such as age, gender, ethnicity, gene-gene interaction and environmental condition are needed to clear the true association of MTHFR polymorphisms with CLL.