A comprehensive consolidation of data on the relationship between IRF6 polymorphisms and non-syndromic cleft lip/palate susceptibility: From 79 case-control studies.

BACKGROUND: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent craniofacial birth defect on a global scale. A number of candidate genes have been identified as having an impact on NSCL/P. However, the association between interferon regulatory factor 6 (IRF6) polymorphisms and NSCL/P has yielded inconsistent results, prompting the need for a meta-analysis to obtain more accurate estimates. METHODS: We conducted a thorough screening of all relevant articles published up until November 15, 2023, in online bibliographic databases. The statistical analysis of the collected data was performed using the Comprehensive Meta-Analysis (Version 4.0) software. RESULTS: A total of 79 case-control studies, comprising 14,003 cases and 19,905 controls, were included in our analysis. The combined data indicated that the IRF6 rs642961 and rs2235371 polymorphisms were associated with an increased risk of NSCL/P in the overall population. However, no significant association was found between the rs2013162 and rs2235375 polymorphisms and the risk of NSCL/P in the overall population. Furthermore, subgroup analyses revealed significant correlations between the IRF6 rs642961, rs2235371, and rs2235375 polymorphisms and the risk of NSCL/P based on ethnic background and country of origin. Nevertheless, the rs2013162 polymorphism plays a protective role in Caucasians and mixed populations. CONCLUSIONS: Our collective data indicates a significant association between the rs642961 and rs2235371 polymorphisms and the risk of NSCL/P in the overall population. The rs2235375 polymorphism could influence the susceptibility to NSCL/P based on ethnic background. Meanwhile, the rs2013162 polymorphism provides protective effects in Caucasian, mixed populations, and the Brazilian population.

Coronary artery disease incidence, risk factors, awareness, and medication utilization in a 10-year cohort study.

BACKGROUND: There is a substantial disparity in coronary artery disease (CAD) burden between Iran and other nations that place a strong emphasis on the assessment of CAD risk factors and individuals' awareness and ability to control them. METHODS: Two thousand participants of a community-based Iranian population aged 20-74 years were investigated with a mean follow-up of 9.9 years (range: 7.6 to 12.2). An analysis of Cox regression was conducted to determine the association between CAD development and classic risk factors such as age, sex, smoking, physical activity, education, obesity, dyslipidemia, hypertension, and diabetes mellitus. Furthermore, we computed the population attributable fraction for these risk factors. RESULTS: After a follow-up period of nearly 10 years, 225 CAD events were reported, constituting 14.5% of the overall incidence. Nighty three percent of participants had more than one risk factor. Age was the most predictive risk factor, with a hazard ratio (HR) and confidence interval (CI) of 5.56 (3.87-7.97, p < 0.001) in men older than 45 and females older than 55 compared to lower ages. In comparison to females, males had an HR of 1.45 (CI: 1.11-1.90, p value = 0.006) for developing CAD. Nearly 80% of the patients had dyslipidemia, with a hazard ratio of 2.19 (CI: 1.40-3.44, p = 0.01). Among the participants, 28.9% had hypertension, and 52% had prehypertension, which had HRs of 4.1 (2.4-7.2, p < 0.001) and 2.4 (1.4-4.2, p < 0.001), respectively. Diabetes, with a prevalence of 17%, had an HR of 2.63 (CI: 2 -3.47, p < 0.001), but prediabetes was not significantly associated with CAD. Awareness of diabetes, dyslipidemia, and hypertension was 81%, 27.9%, and 48.1%, respectively. Regarding medication usage, the corresponding percentages were 51% for diabetes, 13.2% for dyslipidemia, and 41% for hypertension. CONCLUSIONS: Compared to previous studies in Iran and neighboring countries, the current study found a higher incidence of CAD, more prevalent risk factors, and a lower awareness and ability to control these risk factors. Thus, an effective preventive strategy is needed to reduce the CAD burden in Iran.

An innovative model for predicting coronary heart disease using triglyceride-glucose index: a machine learning-based cohort study.

BACKGROUND: Various predictive models have been developed for predicting the incidence of coronary heart disease (CHD), but none of them has had optimal predictive value. Although these models consider diabetes as an important CHD risk factor, they do not consider insulin resistance or triglyceride (TG). The unsatisfactory performance of these prediction models may be attributed to the ignoring of these factors despite their proven effects on CHD. We decided to modify standard CHD predictive models through machine learning to determine whether the triglyceride-glucose index (TyG-index, a logarithmized combination of fasting blood sugar (FBS) and TG that demonstrates insulin resistance) functions better than diabetes as a CHD predictor. METHODS: Two-thousand participants of a community-based Iranian population, aged 20-74 years, were investigated with a mean follow-up of 9.9 years (range: 7.6-12.2). The association between the TyG-index and CHD was investigated using multivariate Cox proportional hazard models. By selecting common components of previously validated CHD risk scores, we developed machine learning models for predicting CHD. The TyG-index was substituted for diabetes in CHD prediction models. All components of machine learning models were explained in terms of how they affect CHD prediction. CHD-predicting TyG-index cut-off points were calculated. RESULTS: The incidence of CHD was 14.5%. Compared to the lowest quartile of the TyG-index, the fourth quartile had a fully adjusted hazard ratio of 2.32 (confidence interval [CI] 1.16-4.68, p-trend 0.04). A TyG-index > 8.42 had the highest negative predictive value for CHD. The TyG-index-based support vector machine (SVM) performed significantly better than diabetes-based SVM for predicting CHD. The TyG-index was not only more important than diabetes in predicting CHD; it was the most important factor after age in machine learning models. CONCLUSION: We recommend using the TyG-index in clinical practice and predictive models to identify individuals at risk of developing CHD and to aid in its prevention.

Autosomal recessive cutis laxa type 1C with a homozygous LTBP4 splicing variant: a case report and update of literature.

BACKGROUND: Autosomal recessive cutis laxa (ARCL) is a heterogeneous disorder with three primary forms (ARCL 1, ARCL 2 and ARCL 3). Latent transforming growth factor beta binding protein 4 (LTBP4) anomalies cause ARCL1C and are connected to different problems in the skin and other organs. Herein, we present a seven month old Iranian boy with a clinical manifestation of ARCL1 with literature review of previous cases with attributes of ARCL1C. METHODS: Considering the craniofacial characteristics and respiratory distress of the proband, cutis laxa (CL) was expected and whole-exome sequencing (WES) was performed. RESULTS: In the proband, signs of CL were mainly located in the face, thorax, and abdomen. The prenatal investigation revealed a diaphragmatic hernia and certain uncommon signs, such as an atrial septal defect and pyloric stenosis. The WES showed a novel homozygous mutation (c.533-1G > A) in exon six of the LTBP4 gene. CONCLUSION: This report showed a new variant with uncommon clinical features, such as a stenosis atrial septal defect and pyloric stenosis, which causes ARCL1C. Unfortunately, the proband developed several heart problems and died at the age of seven months and seven days. Thus, a more in-depth evaluation is needed to clarify the different aspects of CL related to LTBP4 disorder.

Association between Fetal MTHFR A1298C (rs1801131) Polymorphism and Neural Tube Defects Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: The association of the fetal MTHFR A1298C (rs1801131) polymorphism and neural tube defects (NTDs) susceptibility has been widely demonstrated, but the results remain inconclusive. Thus, we performed a meta-analysis to investigate the association between fetal MTHFR A1298C polymorphism and NTDs risk. METHODS: An electronic search of PubMed, web of science, SciELO, CNKI database for studies on the fetal MTHFR A1298C polymorphism and NTDs risk was performed up to March 30, 2020. RESULTS: A total of 22 case-control studies with 3,224 fetuses with NTDs and 3,295 controls were selected. Overall, pooled data showed that the fetal MTHFR A1298C polymorphism was not significantly associated with risk an increased risk of NTDs in the global population. When stratified analysis by ethnicity, country of origin and NTDs type, still no statistically significant association was found. CONCLUSIONS: Our pooled data emerged no evidence for significant association between fetal MTHFR A1298C polymorphism and NTDs risk.

Association of PAI-1 4G/5G and ACE I/D Polymorphisms with Susceptibility to Pediatric Sepsis: Evidence from a Meta-Analysis.

BackgroundSeveral studies have investigated the role of PAI-1 4G/5G and ACE I/D polymorphisms in the etiology of pediatric sepsis, but the results are inconsistent. We performed a meta-analysis to assess for any associations. Methods: A comprehensive literature search on PubMed, web of science, and CNKI database was conducted up to April 15, 2020. Results: There were twelve case-control studies involving seven studies with 860 cases and 1144 controls on PA-1 4G/5G and five studies with 1602 cases and 1585 controls on ACE I/D. PAI-1 4G/5G and ACE I/D polymorphisms were associated with an increased risk of pediatric sepsis in the global population. Stratified analysis by ethnicity showed a significant association in the Caucasians children. Conclusions: The meta-analysis suggests that the PAI-1 4G/5G and ACE I/D polymorphisms may be risk factors for development of pediatric sepsis in the global population.

Association of Fetal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects: A Systematic Review and Update Meta-Analysis.

Background MTHFR gene may be a key epigenetic regulation-related factor crucial during embryogenesis. We performed a meta-analysis to determine the association of fetal MTHFR C677T polymorphism with neural tube defects (NTDs).Methods A comprehensive literature search of the PubMed, Embase, and CNKI database was performed up to April 10, 2020.Results A total of 19 case-control studies with 2,228 NTDs cases and 4,220 controls were identified. Pooled data revealed that the fetal MTHFR C677T polymorphism was significantly highly correlated with development of NTDs in the overall population. Stratified analysis showed a significant association among Caucasians and Asians, but not in mixed populations. There was a significant association between the MTHFR C677T polymorphism and spina bifida risk. No publication bias was found under any genetic model.Conclusions Our pooled data support the fetal MTHFR C677T polymorphism association with risk of NTDs, especially among Caucasians and Asians.

Association of +1923C > T, -1112C > T and +2044A > G Polymorphisms in IL-13 Gene with Susceptibility to Pediatric Asthma: A Systematic Review and Meta-Analysis.

BackgroundPrevious studies have provided conflicting evidence implicating the IL-13 polymorphism and pediatric asthma. Thus, we performed a meta-analysis to combine and analyze the available studies to provide more accurate conclusions. Methods: A comprehensive retrieval in PubMed, EMBASE, Web of Science, and CNKI was performed up to February 05, 2020. Results: A total of 39 case-control studies including 15 studies with 4,968 cases and 7,091 controls were on +1923 C > T, ten studies with 3,175 cases and 2,983 controls on -1112 C > T, and 14 studies with 4,476 cases and 5,121 controls on +2044 A > G were selected. Pooled data showed that the IL-13 + 1923 C > T, -1112 C > T and +2044 A > G polymorphisms were significantly associated with risk of pediatric asthma. The IL-13 + 1923 C > T (Asians and Africans), -1112 C > T (Caucasians) and +2044 A > G (Asians) polymorphisms were more frequently associated in these ethnic groups. Conclusions: Our pooled data indicated that IL-13 + 1923 C > T, -1112 C > T and +2044 A > G polymorphisms were correlated with risk of pediatric asthma.

Meta-analysis of the frequency of intrauterine growth restriction and preterm premature rupture of the membranes in pregnant women with COVID-19

The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pregnancy has yet to be determined. Some studies indicate that SARSCoV- 2 infection may be associated with a higher risk of adverse outcomes in pregnant women. Here, we performed a meta-analysis to estimate the frequency of intrauterine growth restriction (IUGR) and preterm premature rupture of the membranes (PPROM) in pregnant women with Coronavirus disease-2019 (COVID-19). A comprehensive search was performed in various databases, such as PubMed, Scopus, SciELO, MedRxiv, and Web of Science, to find all relevant studies published before 10 February 2021. Cross-sectional and consecutive case series reporting the pregnancy outcomes of COVID-19 were included. A total of 24 studies, including 8 studies on IUGR and 16 studies on PPROM, were selected. Pooled data showed that the frequencies of IUGR and PPROM in pregnant women with COVID-19 were 2.6% and 9.9%, respectively. Analyses stratified by ethnicity showed that the frequencies of IUGR in Asian and Caucasian COVID-19-infected pregnant women were 2.9% and 2.0%, respectively. Moreover, the frequencies of PPROM in Asian and Caucasian COVID-19-infected pregnant women were 10.2% and 5.8%, respectively. This meta-analysis showed that the frequencies of IUGR and PPROM in COVID-19-infected pregnant women were 2.6% and 9.9%, respectively. However, well-designed, large-scale and multicenter clinical studies are required to improve and validate these results.

A meta-analysis for association of eNOS VNTR 4b/a, - 786 T > C and + 894G > T polymorphisms with risk of recurrent pregnancy loss.

BACKGROUND: The association of polymorphisms at nitric oxide synthases (eNOS) gene with recurrent pregnancy loss (RPL) susceptibility has been the focus of attention in several studies. However, the conclusions have been divergent and controversial. Therefore, we performed this study to precisely evaluate the association of eNOS polymorphisms with the risk of RPL. METHODS: A universal search in PubMed, Web of Knowledge, SciELO, MedRxiv, Scopus and web of Science was performed to identify relevant studies up to January 25, 2020. RESULTS: A total of 39 eligible studies including 15 studies with 2274 cases and 1933 controls on VNTR 4b/a, nine studies with 1640 cases and 1268 controls on -786C > T, and 15 studies with 2660 cases and 2557 controls on + 894G > T polymorphism were selected. Pooled data revealed that eNOS VNTR 4b/a (dominant model: OR = 1.174, 95% CI 1.021-1.350, p = 0.025) and + 894G > T (allele model: OR = 1.278, 95% CI 1.024-1.595, p = 0.030; homozygote model: OR = 1.442, 95% CI 1.084-1.917, p = 0.012; dominant model: OR = 1.305, 95% CI 1.006-1.693, p = 0.045; and recessive model: OR = 1.378, 95% CI 1.045-1.817, p = 0.023) polymorphisms were significantly associated with an increased risk of RPL, but not - 786 T > C. Stratified analysis by ethnicity revealed that the eNOS + 894G > T was associated with RPL risk in Asians. CONCLUSIONS: To sum up, our results indicated that the eNOS VNTR 4b/a and + 894G > T polymorphisms might be contributing to RPL development, but not the - 786C > T polymorphism.

Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children.

BACKGROUND AND AIM: The aim of this study was to evaluate the association of MC4R rs17782313 and FTO rs9939609 polymorphisms with childhood obesity. METHODS: A universal search was performed up to May 2021. RESULTS: A total of 31 studies including 13 studies with 9565 cases and 11956 controls on MC4R rs17782313 and 18 studies with 4789 cases and 15918 controls on FTO rs9939609 were selected. CONCLUSIONS: Pooled data showed that FTO rs9930506 and MC4R rs17782313 polymorphisms were significantly associated with obesity in children. Stratified analyses revealed that these genetic variants were associated with childhood obesity in Caucasian and Asian children.

Association of SERPINE1 rs1799889 polymorphism with arterial ischemic stroke in children: a systematic review and meta-analysis.

Inherited thrombophilias are well-established predisposing factors for venous thromboembolism, but their role in arterial ischemic stroke (AIS) in children, remains unclear. The association between SERPINE1 rs1799889 polymorphism and AIS in children was evaluated by several studies, whereas the results were conflicting. Thus, we performed this meta-analysis to combine and analyze the available studies in order to provide a more accurate result on the association. PubMed, Scopus, EMBASE, SciELO, MedRxiv, China Biology Medicine Disk, DeepDyve, CNKI, and Web of Science were used to identify all relevant articles published up to 30 November 2020, without any restrictions on ethnicity. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the strength of the associations. A total of eight case-control studies with 600 cases and 2,156 controls were selected. No significant association between SERPINE1 rs1799889 polymorphism and AIS in children susceptibility was noted. In the stratified analyses by ethnicity, source of controls, genotyping methods, and age groups, there was still no significant association between SERPINE1 rs1799889 polymorphism and AIS risk in children. This study suggested that SERPINE1 rs1799889 polymorphism might be not related to etiology of AIS in children. Moreover, well-designed, large-scale and multicenter clinical studies are required to improve and validate these results.Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1966798 .

A meta-analysis of the association of the ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Iranian women: Are the investigations adequate?

The associations of ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss (RPL) in Iranian women have yielded controversial results. Thus, we conducted a meta-analysis to obtain more certain results. A comprehensive literature search was performed in the PubMed, Web of Sciences, Scopus, MedRxiv, SID, and CNKI databases up to January 1st, 2021, using the appropriate terms. All case-control studies were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 14 studies including eight studies with 783 patients and 761 healthy subjects on ACE I/D and six studies with 1.155 patients and 699 healthy subjects on PAI-1 4G/5G were included. Combined data revealed that ACE I/D polymorphism was significantly associated with RPL risk in Iranian women under three models i.e., allele [OR=0.744, 95% CI: (0.640-0.864); p≤0.001], dominant [OR=0.774, 95% CI: (0.601-0.996); p=0.047], and recessive [OR=0.767, 95% CI: (0.611-0.963); p=0.022]. Moreover, the pooled data showed a significant association between the PAI-1 4G/5G polymorphism and RPL risk under all five models i.e., allele [OR=2.352, 95% CI: (1.623-3.408); p≤0.001], heterozygote [OR=8.364, 95% CI: (4.744-14.756); p≤0.001), homozygote [OR=2.192, 95% CI: (1.093-4.394); p=0.027), dominant [OR=2.354, 95% CI: (1.309-4.235); p=0.004], and recessive [OR=5.208, 95% CI: (3.005-9.025); p≤0.001]. Stratification analysis revealed that these polymorphisms were associated with RPL risk by the number of miscarriages. Our pooled data indicated that ACE I/D and PAI-1 4G/5G polymorphisms were significantly associated with an increased risk of RPL in Iranian women. These significant findings showed that the investigation might be adequate for ACE I/D and PAI-1 4G/5G polymorphisms in the Iranian population.

Association of IL-6 -174G > C Polymorphism with Susceptibility to Childhood Sepsis: A Systematic Review and Meta-Analysis.

BackgroundThis meta-analysis evaluates the correlation between the IL-6 -174 G > C polymorphism and susceptibility of childhood sepsis. Methods: We searched PubMed, ISI Web of Knowledge, Scopus, CNKI, SID, SciELO databases until December 30, 2019 to identify all eligible studies. Results: A total of 17 studies with 1,287 cases and 2,482 controls were identified. Pooled data revealed that there was no significant association between the IL-6 -174 G > C polymorphism and risk childhood sepsis in the overall population. When stratified analysis was carried out by age group of cases, no associations were found in neonates and pediatrics. However, in ethnicity-based subgroups, a significant association was found in Caucasians and Africans. Conclusions: There was no significant association of the IL-6 -174G > C polymorphism with susceptibility to sepsis in childhood overall, but there was an association with the Caucasian and African ethnic subgroups.

Association of MTHFR 677C > T, 1298A > C and MTR 2756A > G Polymorphisms with Susceptibility to Childhood Retinoblastoma: A Systematic Review and Met-Analysis.

BackgroundRecently, epidemiological studies investigating the association of MTHFR 677 C > T, 1298 A > C and MTR 2756 A > G polymorphism with retinoblastoma susceptibility reported controversial results. Methods: Data were collected from several electronic databases such as PubMed, EMBASE, and Google Scholar databases, with the last search up to December 05, 2019. Results: A total of eleven case-control studies including four studies with 324 cases and 490 controls on MTHFR 677 C > T, four studies with 324 cases and 490 controls on MTHFR 1298 A > C, and three studies with 283 cases and 485 controls on MTR 2756 A > G were selected. There was a significant association between MTHFR 677 C > T and MTR 2756 A > G polymorphisms and an increased risk of retinoblastoma. However, MTHFR 1298 A > C polymorphism was not significantly associated with risk of retinoblastoma. Conclusion: This meta-analysis demonstrated that MTHFR 677 C > T and MTR 2756 A > G polymorphisms might play important roles in the development of retinoblastoma. No association with MTHFR 1298 A > C polymorphism was observed.

Cumulative Evidence for Association between IL-10 Polymorphisms and Kawasaki Disease Susceptibility: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis was carried out to evaluate the associations between IL-10 polymorphisms and Kawasaki disease (KD) risk. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, China National Knowledge Infrastructure and SciELO for all relevant studies evaluating IL-10 polymorphism and susceptibility to KD. The associations were measured by odds ratios (ORs) and its corresponding 95% confidence intervals (CIs). RESULTS: A total of 13 studies including four studies on -1082 A > G, four studies on -819 T > C and five studies on -592 A > C polymorphism were selected. Pooled data revealed that IL-10 -592 A > C polymorphism was significantly associated with an increased risk of KD (C vs. A: OR = 0.402, 95% CI 0.194-0.832, p = 0.014). However, IL-10 -1082 A > G and -819 T > C polymorphisms were not significantly associated with risk of KD under all five genetic models. CONCLUSIONS: Our results revealed that IL-10 -592 A > C polymorphism was associated with risk of KD, while IL-10 -1082 A > G and -819 T > C polymorphisms were not involved in the development of KD.

An Updated and Comprehensive Meta-Analysis of Association between VEGA -634G > C, -460T > C, +405G > C and +936C > T Polymorphisms and Retinopathy of Prematurity Risk.

BACKGROUND: Previous studies have suggested an association between VEGF-A polymorphisms and retinopathy of prematurity (ROP) risk. But the conclusions are still controversial. The aim of this meta-analysis was to evaluate the association between the VEGF-A polymorphisms and susceptibility of ROP. Methods: We searched PubMed, Scopus, WanFang and CNKI databases for all eligible case-control studies published before September 30, 2019. Results: A total of 27 case-control studies with 5,748 ROP cases and 6,146 controls were selected. The results suggested that there was an association between VEGF-A -460T > C polymorphism and increased risk of ROP under the allele model (C vs. T: OR= 0.879, 95% CI 0.776-0.994, p = 0.040). However, VEGF-A -634G > C, +405G > C and +936C > T polymorphisms were not significantly associated with risk of ROP. The subgroup analysis demonstrated that VEGF-A +405G > C polymorphism was associated with ROP risk in Caucasians. Conclusions: This meta-analysis indicates that VEGF-A -460T > C polymorphism may contribute to the susceptibility for ROP.

Association of Fetal MTHFR 677C > T Polymorphism with Non-Syndromic Cleft Lip with or without Palate Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: This study was conducted to estimate the precise association of fetal MTHFR 677 C > T polymorphism with risk of nonsyndromic cleft lip with or without cleft palate (NSCL ± P) using a large-scale meta-analysis. Methods: A comprehensive literature search was performed using studies published on PubMed, Science Direct, Scopus and CNKI databases up to November 1, 2019. Results: A total of 38 studies with 6,525 children with NSCL ± P and 8,606 controls were selected. Overall, there was a significant association between MTHFR 677 C > T polymorphism and NSCL ± P risk. Subgroup analysis by ethnicity revealed that MTHFR 677 C > T polymorphism contributed to development of NSCL ± P in Caucasian and Mixed populations, but not in Asians. When stratified by country of origin, we found a significant association in Brazilian, Turkish and Indian populations, but not in Chinese and US-American. Conclusions: This meta-analysis provides strong evidence that fetal MTHFR 677 C > T polymorphism is significantly associated with NSCL ± P risk.

Association of TNF-α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 Polymorphisms with Susceptibility to Kawasaki Disease: A Comprehensive Meta-Analysis.

BACKGROUND: Kawasaki Disease (KD) is a multifactorial condition at the junction of infectious diseases, immunology, rheumatology, and cardiology. The aim of this study is to derive a more precise estimation of the association of TNF-α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 polymorphisms with risk of KD. Methods: PubMed, EMBASE, CNKI databases were searched to identify all relevant studies. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using CMA 2.2 software. Results: A total of 25 studies including eleven studies on TNF-α rs1800629, five studies on CASP3 rs72689236 and nine studies on FCGR2A rs1801274 were selected. Overall, pooled data revealed that CASP3 rs72689236 and FCGR2A rs1801274 polymorphisms were significantly associated with an increased risk of KD. However, there was no significant association between TNF-α rs1800629 and KD. Conclusions: This meta-analysis suggested that CASPS rs72689236 and FCGR2A rs1801274 polymorphisms may modulate individual susceptibility to KD.

Association of MTHFR 1298A > C Polymorphism with Susceptibility to Non-Syndromic Cleft Lip with or without Palate: A Case-Control Study and Meta-Analysis.

BACKGROUND: Several studies have evaluated association of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene 1298A > C polymorphism with non-syndromic cleft lip with or without palate (NSCL ± P) susceptibility, however the results are inconsistent. MATERIALS AND METHODS: To address this issue, we performed a case-control study to evaluate the association of MTHFR 1298A > C polymorphism with NSCL ± P risk, followed by a meta-analysis. RESULTS: Including our study, a total of 22 case-control studies with 2,814 cases and 4,199 controls were selected. The results suggested that there was no significant association between MTHFR 1298A > C polymorphism and NSCL ± P risk overall. The subgroup analysis demonstrated that the polymorphism was significantly associated with NSCL ± P risk in Asians and Iranian populations, but not in Caucasians, mixed and Chinese populations. CONCLUSION: This meta-analysis indicates that MTHFR 1298A > C polymorphism may not contribute to NSCL ± P risk in overall. However, the MTHFR 1298A > C polymorphism was significantly associated with an increased risk of NSCL ± P in Asians and Iranian populations.