Homozygote Model Research Articles

A Meta-analysis of Pin1 gene polymorphism at -842 loci and cancer susceptibility

Objective: Using Meta-analysis to evaluate the association between Pin1 gene polymorphism at -842 loci and cancer susceptibility. Methods: Pin1, polymorphism, tumor, variant and cancer as key words were used to systematically search for the case-control research on the association between the -842G/C polymorphisms of Pin1 and cancer susceptibility through China National Knowledge Infrastructure (CNKI), Wanfang Data, Embase and PubMed. The time of literatures was up to April 2(nd), 2019. Heterogeneity test, combined risk of cancer with the -842 C allele of Pin1, publication bias test and sensitivity analysis were performed by using Stata 12.0 software. Results: A total of 144 articles were retrieved. According to the inclusion criteria, a total of 11 articles were included (2 Chinese documents and 9 English documents). There were 5 667 cases and 6 120 controls in eligible articles. The heterozygous model showed that Pin1 (-842G/C) polymorphism was associated with cancer susceptibility, and the pooled OR (95%CI) value was 0.78 (0.61, 0.99). Subgroup analysis by cancer type suggested that the Pin1 (-842G/C) polymorphism could significantly decrease the incidence of breast cancer and lung cancer under the heterozygous model (GC vs GG), dominant model (GC+CC vs GG) and allele model (C vs G). The pooled OR (95%CI) values were 0.73 (0.58, 0.92), 0.71 (0.57, 0.89), and 0.73 (0.60, 0.89) in breast cancer and 0.64 (0.52, 0.78), 0.64 (0.53, 0.78), and 0.67 (0.55, 0.80) in lung cancer. The variant -842 C allele could significantly increase the risk of nasopharyngeal carcinoma under the homozygote model (CC vs GG) and recessive model (CC vs GG+GC). The pooled OR (95%CI) values were 2.22 (1.03-4.75) and 2.47 (1.16-5.26). No significant association was observed in squamous cell carcinoma. Conclusion: This Meta-analysis demonstrated that Pin1gene polymorphism at -842 was associated with cancer susceptibility.

A meta-analysis and meta-regression of association between MTHFR A1298C polymorphism and nonsyndromic cleft lip/palate risk: An evaluation based on five genetic models

The present meta-analysis is intended to assess the association between NSCL/P risk and methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism in case-control studies. The Web of Science, PubMed/Medline, Scopus, and Cochrane Library databases were searched for related articles published by April 2019. Review Manager 5.3 was applied to measure the odds ratios (ORs) with 95% confidence interval (CI) in the analyses assessing the strength of the association between A1298C polymorphism and NSCL/P risk. Results Sixteen studies were involved and analysed in this meta-analysis. Altogether, the reviewed articles included 2677 NSCL/P patients and 3669 controls. The pooled ORs of the allele, homozygote, heterozygote, dominant, and recessive models were 1.11 (95% CI: 0.94, 1.30; P=0.21), 1.14 (95% CI: 0.94, 1.37; P=0.18), 0.98 (95% CI: 0.80, 1.20; P=0.87), 1.03 (95% CI: 0.86, 1.22; P=0.79), and 1.18 (95% CI: 0.99, 1.41; P=0.07), respectively. The analysis did not identify any significant association between the polymorphism and the risk of NSCL/P in any ethnicity or source of controls. This meta-analysis revealed that A1298C polymorphism is not associated with NSCL/P susceptibility, and the subgroup analyses based on ethnicity and the source of cases further confirmed this result.

Association of Paraoxonase 1 Gene Polymorphisms and Polycystic Ovarian Syndrome Susceptibility: A Systematic Review and Meta-Analysis

Introduction: The goal of this study was to review relevant case-control trials in order to determine the association of paraoxonase 1 (PON1) gene polymorphisms (–108C/T, 55L/M, 192Q/R) and polycystic ovarian syndrome (PCOS) susceptibility. Methods: Using appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through April 2019 were considered for inclusion. Based on the qualified studies, we performed a meta-analysis of associations between –108C/T, 55L/M and 192Q/R polymorphisms in PON1 and risk of PCOS. Results: We included 13 case-control studies with 3,660 total patients in the PCOS group and 2,835 in the control group. These studies found that the population with –108C/T locus T were associated with lower PCOS susceptibility by heterozygote model (OR 0.442, 95% CI 0.259–0.754); the Caucasian population with –108C/T locus T were associated with higher PCOS susceptibility by regressive model (OR 2.087, 95% CI 1.242–3.504). The population with 55L/M locus M were associated with higher PCOS susceptibility by regressive model (OR 1.518, 95% CI 1.067–2.160); the Asian population with 55L/M locus M were associated with lower PCOS susceptibility by dominant model and heterozygote model. The population with 192Q/R locus R were associated with higher PCOS susceptibility by the 5 gene models. The Asian population with 192Q/R locus R were associated with higher PCOS susceptibility: allelic model (OR 1.271, 95% CI 1.139–1.417); homozygote model (OR 1.575, 95% CI 1.244–1.995); dominant model (OR 1.299, 95% CI 1.069–1.580); regressive model (OR 1.421, 95% CI 1.207–1.673). The Caucasian population with 192Q/R locus R were associated with higher PCOS susceptibility: heterozygote model (OR 2.113, 95% CI 1.266–3.526). Conclusion: Our meta-analysis suggested that 192Q/R locus R were associated with higher PCOS susceptibility in both the Asian and Caucasian population.

Methylenetetrahydrofolate reductase C677T polymorphism is not associated with the risk of nonsyndromic cleft lip/palate: An updated meta-analysis

Both genetic and environmental factors affect the risk of orofacial clefts. The present meta-analysis aimed to evaluate the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of nonsyndromic cleft lip/palate (NSCL/P) in cases-control studies. The PubMed/Medline, Scopus, Web of Science, and Cochrane Library databases were searched up to April 2019 with no restrictions. The odds ratios (ORs) and 95% confidence intervals (CIs) in all analyses were calculated by Review Manager 5.3 software. The funnel plot analysis was carried out by the Comprehensive Meta-Analysis version 2.0 software. Subgroup analysis, meta-regression, and sensitivity analysis were performed for the pooled analyses. Thirty-one studies reviewed in this meta-analysis included 4710 NSCL/P patients and 7271 controls. There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility related to allelic model (OR = 1.04; P = 0.49), homozygote model (OR = 1.11; P = 0.35), heterozygote model (OR = 0.99; P = 0.91), dominant model (OR = 1.00; P = 0.96), or recessive model (OR = 1.08; P = 0.23). There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility based on the ethnicity or the source of cases. There was a significant linear relationship between the year of publication and log ORs for the allele model. The results of the present meta-analysis failed to show an association between MTHFR C677T polymorphism and NSCL/P susceptibility. The subgroup analyses based on the ethnicity and the source of cases further confirmed this result.

A Meta-analysis Assessing the Association Between COL11A1 and GDF5 Genetic Variants and Intervertebral Disc Degeneration Susceptibility

Meta-analysis to collect relevant studies to assess the association between COL11A1 and GDF5 genetic variants and susceptibility to IDD. The aim of this study was to assess whether or not COL11A1 and GDF5 genetic variants were associated with susceptibility to IDD. IDD or LDH is a major public health problem. There have been several studies evaluating the relationship between COL11A1 and GDF5 genetic variants with risk of intervertebral disc degeneration (IDD). However, the studies were limited in discrete outcome and sample size, and some of the results were contradictory. We systematically searched the relevant publications in electronic databases. Eligible studies were included based on the defined criteria. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were received using STATA 15. Subgroup analysis, sensitivity analysis, publication bias, and the "Trim and fill" method were performed in the meta-analysis. A total of 3287 IDD cases and 5115 controls were incorporated into the meta-analysis. Our results demonstrated that COL11A1 rs1676486 was significantly associated with increased IDD susceptibility under all genetic models (allele model T vs. C: OR = 1.40, 95% CI 1.23-1.59, P = 0.000; homozygote model TT vs. CC: OR = 1.89, 95%CI 1.40-2.56, P = 0.000; dominant model TT+TC vs. CC: OR = 1.52, 95% CI 1.29-1.80, P = 0.000; recessive model TT vs. TC + CC: OR = 1.58, 95% CI 1.18-2.12, P = 0.002). However, GDF5 rs143383 was not (allele model T vs. C: OR = 1.15, 95% CI 0.91-1.44, P = 0.244; homozygote model TT vs. CC: OR = 1.22, 95% CI 0.75-2.00, P = 0.429; dominant model TT vs. CC+CT: OR = 1.22, 95% CI 0.95-1.57, P = 0.112; recessive model TC + TT vs. CC: OR = 1.12, 95% CI 0.73-1.73, P = 0.594). Subgroup analysis indicated ethnicity was not the source of heterogeneity. Sensitivity analysis, publication bias, and the "Trim and fill" method demonstrated the meta-analysis was of reliability. Our results suggested that COL11A1 rs1676486 was significantly associated with IDD and the T allele was a risky factor. However, GDF5 rs143383 was not. 1.

Association of microRNA gene polymorphisms with Type 2 diabetes mellitus: A systematic review and meta-analysis.

Background:Type 2 diabetes mellitus (T2DM) is a metabolic disorder with growing prevalence and increasing economic burden. Based on the role of genetics and epigenetic factors on T2DM, we aimed to carry a systematic review and meta-analysis for all miRNA gene polymorphisms and risk of T2DM.Materials and Methods:A computerized literature search was carried out on PubMed, Web of Science, Scopus, Embase, as well as references of relevant review/meta-analysis. Key search terms were “Diabetes Mellitus, Type 2,” “MicroRNAs,” and “Polymorphism, Single Nucleotide.” All types of observational studies from January 1, 1992, to November 30, 2019, were included, without language restriction. Data analysis was performed using R programming language (3.5.2). Level of heterogeneity was obtained by Cochran's Q test (P < 0.05), and subgroup analysis was performed based on ethnicity.Results:Thirty-two polymorphisms from fifteen articles were included. Meta-analysis was carried out based on minor allele frequencies. Seven studies with 2193 cases and 3963 controls were included for rs2910164 polymorphism. In subgroup analysis, there were significant results in Caucasian population in dominant model (odds ratio [OR] =1.12; 95% confidence interval [CI]: 0.83–1.51), homozygote model (OR = 1.78; 95% CI: 1.06–3.00), heterozygote model (OR = 1.77; 95% CI: 1.03–3.05), and recessive model (OR = 1.78; 95% CI: 1.07–2.96). Four studies with 2085 cases and 1933 controls were included for rs895819 polymorphism. Overall, there was no significant result for association with rs895819, but subgroup analysis revealed that minor allele significantly decreased the risk of T2DM in Caucasians by recessive model (OR = 0.34; 95% CI: 0.18–0.66), dominant model (OR = 0.70; 95% CI: 0.52–0.94), homozygote model (OR = 0.32; 95% CI: 0.16–0.62), heterozygote model (OR = 0.37; 95% CI: 0.19–0.74), allelic model (OR = 0.67; 95% CI: 0.52–0.85).Conclusion:The minor allele of rs2910164 may increase the risk of T2DM by leading to lower level of miR-146a. In contrast, minor allele of rs895819 may decrease the risk of T2DM by leading to higher level of miR-27a.

The Impact of CYP24A1 Polymorphisms on Hypertension Susceptibility

Background: Hypertension is one of the leading causes of human death and disability. CYP24A1 regulates vitamin D activity and is closely linked to hypertension. However, the relationship between CYP24A1polymorphisms and hypertension risk remains unclear. Methods: This case-control study included 503 hypertensive patients and 498 healthy controls from the Chinese Han population. The genotypes of CYP24A1polymorphisms were detected using the Agena MassARRAY method. The association between genetic variations of CYP24A1and hypertension risk was evaluated with odds ratios (OR) and 95% confidence intervals (CI) in genetic models. Results: We found that rs56229249 of CYP24A1significantlydecreased the hypertension risk in homozygote (OR 0.51, 95% CI 0.29–0.91, p = 0.022) and recessive models (OR 0.51, 95% CI 0.29–0.91, p = 0.023). Further stratification analyses indicated that hypertension risk is related to age and sex, rs2762934 polymorphism increases hypertension risk among younger subjects (<61 years), and rs1977297 influences the risk of hypertension among older subjects (≥61 years). In addition, rs2762940 is related to hypertension risk in men, and rs56229249 is a protective factor against hypertension in women. Conclusions: Our study suggests that genetic variations of the CYP24A1gene were significantly associated with susceptibility to hypertension in the Chinese population.

Association of PON1-L55M Genetic Variation and Breast Cancer Risk: A Case-Control Trial.

Background:Paraoxonase 1 (PON1), a multifactorial antioxidant enzyme, has a defensive role against oxidative stress, which is believed to contribute to cancer development. This study aimed to investigate the association of PON1-L55M functional polymorphism with breast cancer risk. Material and methods:In the experimental study, blood samples were collected from 150 healthy women controls and 150 breast cancer subjects. The L55M genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results:Our analysis showed that the genotypes distribution is in Hardy-Weinberg equilibrium for both case and control groups. Our data revealed that there are significant associations between PON1-L55M polymorphism and breast cancer risk in homozygote (OR= 2.13, 95%CI= 1.14-4.00, p= 0.018), dominant (OR= 1.72, 95%CI= 1.07-2.76, p= 0.024), and allelic (OR= 1.55, 95%CI= 1.12-2.15, p= 0.008) models. Conclusions:Our results suggest that the PON1-L55M genetic variation could be a genetic risk factor for breast cancer risk and it could be considered as a molecular biomarker for screening of susceptible women.

Catechol-O-methyltransferase gene Val158Met polymorphism and obsessive compulsive disorder susceptibility: a meta-analysis.

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that affects approximately 1-3% of the general population. It is characterized by disabling obsessions (intrusive unwanted thoughts) and/or compulsions (ritualized repetitive behaviors). Catechol-O-methyltransferase (COMT) enzyme has an important role in inactivation of dopamine and higher dopamine levels may be implicated in OCD, hence COMT gene is a suitable candidate for OCD. Several case-control studies have evaluated the role of COMT Val 158Met (rs4680;472G- > A) polymorphism as a risk factor for OCD but the results remained inconclusive, hence present meta-analysis was designed to find out correct assessment. All studies that investigated the association of COMT gene Val158Met polymorphism with OCD risk, were considered in the present meta-analysis. Statistical analysis was performed with the software program MetaAnalyst. In the current meta-analysis, 14 case-control studies with 1435 OCD cases and 2753 healthy controls were included. The results indicated significant association between COMT Val158Met polymorphism and OCD risk using allele contrast, homozygote and dominant models (ORA vs G = 1.14; 95% CI = 1.02-1.27; p = 0.01; ORAAvs.GG = 1.33; 95% CI = 1.09-1.62, p = 0.004; ORAA + AGvs.GG = 1.14; 95% CI = 1.0-1.32; p = 0.04). In subgroup analysis based on case gender, meta-analysis of male cases showed significant association using all five genetic models (ORAAvsGG = 1.99; 95%CI = 1.42-2.59; p = <0.001; ORAA + AGvs.GG = 1.59; 95% CI = 1.20-2.10; p = 0.001), but did not show any association between COMT Val 158Met polymorphism and OCD risk in females. In conclusion, results of present meta-analysis supports that the COMT Val158Met polymorphism is a risk factor for OCD especially for males.

Association between RFC1 A80G polymorphism and the susceptibility to nonsyndromic cleft lip with or without cleft palate: a meta-analysis.

Reduced folate carrier 1 (RFC1) gene is a candidate for susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P). Association between RFC1 A80G polymorphism and NSCL/P have been studied. The published results are conflicting. A meta-analysis of the association between RFC1 A80G polymorphism and NSCL/P was carried out using Stata13.0. A systematic literature search was performed through the PubMed, EMBASE, the Cochrane Library, Web of Science, ScienceDirect, EBSCOhost, China Biology Medicine databases, China National Knowledge Infrastructure and the Wanfang databases. All relevant studies up to 9 September 2019 were identified. Nine case-control studies including 4,229 total participants (1,334 NSCL/P children, 1,515 healthy children, 656 mothers of the NSCL/P children, and 724 mothers of healthy control children) were included in this study. The meta-analysis revealed that two genetic models of RFC1 A80G polymorphism in NSCL/P children increased risk of NSCL/P: the homozygote model (GG vs. AA, OR =2.346, 95% CI: 1.127-4.884) and the recessive model (GG vs. AG + AA, OR =1.503, 95% CI: 1.049-2.152). Further sensitivity analysis indicated that the frequency of G allele and GG genotype in NSCL/P children was significantly higher than those in the control. However, there was no significant statistical differences after Bonferroni correction. Subgroup analyses indicated the presence of the association of all the model with NSCL/P risk in the Indian children. RFC1 A80G polymorphism in the maternal population of NSCL/P children was not significantly associated with children NSCL/P. The RFC1 A80G polymorphism was a candidate for susceptibility to NSCL/P in the Indian pediatric population. More studies with larger samples are necessary to reach more conclusive outcomes.

Interleukin-6 gene polymorphisms and susceptibility to liver diseases

Background:Several studies have explored the associations between interleukin-6 (IL-6) gene polymorphisms and the susceptibility to liver diseases, however, results remain ambiguous. The goal of this study was to conduct a meta-analysis to provide more credible evidence.Methods:Studies identified in the PubMed, Cochrane Library, and EMBASE databases were used to perform a meta-analysis via the STATA software. Pooled odds ratios (OR) were calculated under fixed- and random-effects models to estimate the potential genetic associations.Results:Twenty-five case-control studies involving 5813 cases and 5298 controls were included in this meta-analysis. Overall, the pooled results suggested that rs1800795 polymorphism was significantly associated with the risk of liver diseases in heterozygote (GC vs CC; OR = 1.57) and dominant (GG+GC vs CC: OR = 1.47) models; rs1800796 polymorphism was significantly associated with the susceptibility to liver diseases in heterozygote (GG vs GC; OR = 0.58) and recessive (GG vs GC+CC: OR = 0.68) models; rs1800797 polymorphism was significantly associated with genetic predisposition to liver diseases in homozygote (GG vs AA: OR = 1.63), heterozygote (GA vs AA; OR = 1.53) and dominant (GG + GA vs AA: OR = 1.61) models. A similar conclusion was found in the HBV, HCV, HCC, NASH and alcoholic liver disease of all ethnic populations for rs1800795; HBV and Asian subgroups for rs1800796; HCV and non-Asian subgroups for rs1800797. However, IL-6 rs2069837 and rs2066992 polymorphisms did not exhibit significant associations with the risk of liver diseases under any genetic models.Conclusion:This meta-analysis suggests that patients carrying G (rs1800795), C (rs1800796) or G (rs1800797) allele or genotypes of IL-6 may be more likely to suffer from liver diseases, which was ethnic-dependent.

Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson's disease: an updated meta-analysis of 41,811 patients.

Parkinson's disease (PD) is one of the most common forms of neurodegenerative disorders, and its etiology remains unclear. Single nucleotide polymorphisms (SNPs) of alpha-synuclein (SNCA) have been found to be significantly associated with PD risk. In particular, the variant rs11931074 was found in one meta-analysis to appear to play a role in the occurrence of PD. This finding has been questioned in subsequent studies, however. The aim of this study was to determine the relationship between PD risk and rs11931074 polymorphism. We performed a systematic online search, including PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI (China National Knowledge Infrastructure), aiming to identify case-control studies looking at the role of rs11931074 in PD. We performed calculations of pooled odds ratio (OR) and 95% confidence interval (95% CI) to assess the associations, and subgroup meta-analyses to verify differences between various ethnicities of different study populations. A total of 13 studies involving 13,403 cases and 28,408 controls met the inclusion criteria after assessment by two reviewers. Overall, there exists significant associations between SNCA rs11931074 polymorphism and the risk of PD under five genetic models (allele contrast model: T vs. G, OR = 1.28, 95% CI = 1.12-1.45, P = 0.0001; homozygote model: TG vs. GG, OR = 1.55, 95% CI = 1.17-2.05, P = 0.002; heterozygote model (TT vs. GG, OR = 1.23, 95% CI = 1.05-1.42, P = 0.009; dominant model: TG+TT vs. GG: OR = 1.25, 95% CI = 1.05-1.50, P = 0.01 and recessive model: TT vs. TG+GG: OR = 1.40, 95% CI = 1.18-1.68, P = 0.0002). When ethnicities were stratified, significant associations were found in the allelic, homozygote, and recessive models for Asians, and in the allelic model for Caucasians. SNCA rs11931074 polymorphism is found to be associated with PD risk and this risk appears to be influenced by genetic status and ethnicity.

Association between dectin-1 gene single nucleotide polymorphisms and fungal infection: a systemic review and meta-analysis.

Objectives: To investigate the association between dectin-1 gene single nucleotide polymorphisms (SNPs) and susceptibility to fungal infection (FI). Methods: Databases were searched electronically and manually to identify case–control studies concerning dectin-1 SNPs and FI, which were published up to 12 November 2018. The Newcastle–Ottawa Quality Assessment Scale was used to determine the study quality and bias. The SNP frequencies of the B (the variant or minor allele) and A (the wild or major allele) alleles of the dectin-1 gene in both cases and controls were analyzed with regard to FI susceptibility. Results: Eight high-quality studies were included in the review. Systemic review of the included studies demonstrated that dectin-1 SNPs rs3901533 and rs7309123 might be associated with susceptibility to invasive pulmonary aspergillosis infection; moreover, rs16910527 SNP can possibly increase the susceptibility to oropharyngeal candidiasis in HIV-positive patients. The meta-analysis identified significant associations between dectin-1 SNPs and overall FI risk in the homozygote model (pooled odds ratio (OR) 1.77, P=0.04). When classified by subtypes, significant associations were also found for deep FI in the homozygote model (pooled OR 2.46, P=0.01) and the recessive model (pooled OR 2.85, P=0.002). There appeared to be no significant association between dectin-1 SNPs and superficial FI. Conclusion: Systemic review of the included studies suggested that dectin-1 SNPs rs3901533, rs7309123, and rs16910527 might play a role in FI susceptibility. The meta-analysis provided convincing evidence that dectin-1 SNPs might have an important role in FI susceptibility, especially for deep FI.

Associations between tumor necrosis factor-α and interleukin-6 polymorphisms and unexplained recurrent spontaneous abortion risk: A meta-analysis.

To evaluate the associations between Tumor necrosis factor-α (TNF-α)(-238G>A) and Interleukin-6 (IL-6)(-174G>C) polymorphism and risk of unexplained recurrent spontaneous abortion (URSA).Correlated case-control studies were collected by computer retrieval. A meta-analysis was conducted by Stata 12.0 software to analysis the strength of association between polymorphism of TNF-α -238G>A and IL-6 -174G>C and URSA.Twenty-one articles with twenty-two studies were included, of which 12 and 10 studies were respectively related to mutation of TNF-α -238G>A, IL-6 -174G>C and URSA. The integrated results showed that the TNF-α-238G>A gene mutation was significantly correlated with the risk of URSA under homozygote model (AA vs GG;OR 1.533,95% CI 1.022–2.301) and recessive model (AA vs GG+AG;OR 1.571,95%CI 1.050–2.350)(P < .05). There was no association between URSA and TNF-α -238G>A under heterozygote model (AG vs GG;OR 0.963,95% CI 0.816–1.137), dominant model (AA+AG vs GG; OR 1.031,95%CI 0.880–1.209) and additive model (A vs G;OR 1.046,95%CI 0.909–1.203)(P > .05). The results of subgroup analysis based on ethnicity showed that -238G>A was significantly correlated with the risk of URSA in Asians under all gene models except for heterozygote model (AG vs GG; OR 1.129,95% CI 0.857–1.487) (P < .05). In Caucasians, it was dominant model (AA+AG vs GG; OR 1.430,95%CI 1.040–1.965) (P < .05) rather than others that showed relationship with URSA. From the integrated results, association was manifested between -174G>C and URSA under all gene models (P < .05) except for recessive model (CC vs GG+CG, OR 1.166, 95%CI 0.938–1.449) (P > .05), which is identical to subgroup analysis based on ethnicity.It is of great guiding significance for screening out and preventing URSA among high-risk women to test on TNF-α -238G>A and IL-6 -174G>C under gene models mentioned above which are highly associated with the risk of URSA, which can act as biological markers for URSA.

Association between interleukin-8 gene -251 A/T polymorphism and the risk of coronary artery disease: A meta-analysis.

Background:The association between interleukin-8 (IL-8) gene polymorphism −251 A>T and susceptibility to coronary artery disease (CAD) has been investigated previously; however, results remain controversial. Thus, a meta-analysis was conducted to reassess the effects of this polymorphism on CAD risks.Methods:The PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies published up to December, 2018. The pooled odds ratios (OR) were calculated using STATA 13.0 software for allelic (A vs T) as well as homozygote (AA vs TT), heterozygote (AT vs TT), recessive (AA vs AT + TT), and dominant (AA + AT vs TT) genotype models, respectively.Results:Ten case-control studies (3744 cases and 3660 controls) were included. Overall, a significant association of IL-8 gene −251 A > T polymorphism with an increased risk of CAD was only observed in the dominant genotype model (OR = 1.48), but not others. In the subgroup analysis, significantly increased risks were also found for Chinese (OR = 1.64), polymerase chain reaction-restriction fragment length polymorphism genotyping (OR = 1.61), acute coronary syndrome (ACS) type (OR = 1.92 for 3 datasets; OR = 1.88 for 4 datasets), high quality (OR = 1.64), and age/gender matching status (OR = 1.55) under the dominant model. Furthermore, significantly increased risks were also found for ACS type under allelic (OR = 1.32 for 3 datasets; OR = 127 for 4 datasets), homozygote (OR = 1.64 for 3 datasets; OR = 1.50 for 4 datasets), heterozygote (OR = 1.32 for 3 datasets; OR = 1.30 for 4 datasets), and recessive (OR = 1.40 for 3 datasets; OR = 1.28 for 4 datasets) models.Conclusion:This meta-analysis suggests that Chinese patients carrying −251A allele of IL-8 may have an increased risk for the development of CAD, especially ACS.

The MMP-8 rs11225395 Promoter Polymorphism Increases Cancer Risk of Non-Asian Populations: Evidence from a Meta-Analysis.

This meta-analysis aimed to systematically review the evidence on cancer risk of the MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model (OR = 1.11, 95% CI: 1.04–1.19), homozygote model (OR = 1.22, 95% CI: 1.05–1.41), heterozygote model (OR = 1.21, 95% CI: 1.07–1.36), and dominant model (OR = 1.21, 95% CI: 1.08–1.35). However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations.

Association between the IL-10 rs1800872 polymorphisms and periodontitis susceptibility: A meta-analysis.

Periodontitis is a common disease with an unclear pathological mechanism. No precise consensus has been reached to evaluate the association between the IL-10 rs1800872 (- 592, -590, -597 C>A) polymorphism and periodontal disease. Thus, we performed this meta-analysis to collect more evidence-based information. Four online databases, PubMed, Embase, Web of Science, and China Biology Medicine disc (CBM), were searched in August 2018. An odds ratio (OR) with a 95% confidence interval (CI) was applied to evaluate the association of the rs1800872 with periodontitis susceptibility. Twenty three case-control studies with 2714 patients and 2373 healthy controls were evaluated. The overall analyses verified that the IL-10 rs1800872 polymorphism was significantly associated with an increased risk of periodontitis in the allelic model, homozygote model, dominant model, and recessive model (A vs C: OR = 1.28, 95%CI = 1.11-1.49, P = .00, I = 56.87%; AA vs CC: OR = 2.06, 95%CI = 1.32-3.23, P = .00, I = 73.3%; AA + AC vs CC: OR = 1.42, 95%CI = 1.03-1.96, P = .03, I = 76.2%; AA vs AC + CC: OR = 1.78, 95%CI = 1.26-2.56, P = .00, I = 76.7%). Moreover, the subgroup analysis based on ethnicity, periodontitis type, and smoking status showed significant differences. The results of our meta-analysis demonstrate that rs1800872 is associated with periodontitis susceptibility in Caucasians and Asians. Moreover, A allele, AA genotype, CC genotype may be closely associated with chronic periodontitis (CP), while A allele, AA genotype may be closely associated with aggressive periodontitis (AgP).

The association of two common polymorphisms in miRNAs with diabetes mellitus: A meta-analysis.

Background:MicroRNAs (miRNAs) are small noncoding single-stranded RNAs with a length of ∼21 nucleotides. Single nucleotide polymorphisms (SNPs) may affect the function of miRNAs, resulting in a variety of disorders in vivo. Recently, diabetes mellitus (DM) has become a global healthcare problem, and several studies have reported that 2 common polymorphisms (miRNA 146a rs2910164 and miRNA 27a rs895819) are related to susceptibility to diabetes. Given that no consensus had been reached regarding the association of the 2 polymorphisms with diabetes, we conducted this meta-analysis.Methods:Four databases (PubMed, EMBASE, Cochrane, and Web of Science) were searched up to January 9, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association strength. Subgroup and sensitivity analyses were also performed.Results:Six studies involving 2585 cases and 2435 controls for miR146a rs2910164 and 5 studies involving 2922 cases and 2781 controls for miR27a rs895819 were ultimately analyzed in our meta-analysis. Based on pooled results, no statistical significance in association between rs2910164 and diabetes in Caucasians, Asians, or type 2 diabetes was observed in any genetic models. Nevertheless, we found a significant correlation between miRNA27a rs895819 and diabetes in the homozygote model (CC vs TT: OR = 0.58, 95%CI [0.35,0.98]) and recessive model (CC vs CT + TT: OR = 0.59, 95%CI [0.36,0.97]). By performing subgroup analysis, we also observed that C allele conveyed a significant protective effect against diabetes development in Caucasians (C vs T: OR = 0.67, 95%CI [0.52,0.85]).Conclusion:In conclusion, this meta-analysis indicated that miRNA27a rs895819 might play a protective role in diabetes, and miRNA146a rs2910164 likely had no association with diabetes.

Relationship between the IL-10 (−1082 A/G) polymorphism and the risk of immune/idiopathic thrombocytopenic purpura: A meta-analysis

BackgroundThe association of the IL-10 gene polymorphism with immune thrombocytopenic purpura (ITP, also called idiopathic thrombocytopenic purpura) susceptibility has been investigated in several studies; however, the association remains controversial. The present meta-analysis aimed to determine whether the IL-10 (−1082) polymorphism is associated with an increased risk of ITP. Materials and methodsEligible articles were searched in EMBASE, PubMed, CNKI, WanFang, and HuGE Navigator, without any restriction of publication language. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to identify any potential associations between the IL-10 (−1082 A/G) polymorphism and the risk of ITP. ResultsThis meta-analysis included six eligible studies with 384 cases and 409 controls. There was no significant association between the IL-10 (−1082) polymorphism and the risk of ITP in any of the genetic models. Three subgroups were stratified according to population ethnicity, disease subtype (acute or chronic), and age (child or adult). No statistically significant differences were observed in age and ethnicity between cases and controls. However, subtype analysis indicated significant associations for acute ITP in the allele model (OR = 1.76, 95% CI = [1.07; 2,89]), the recessive model (OR = 2.66, 95% CI = [1.17; 6.07]), and the homozygote model (OR = 2.65, 95% CI = [1.07; 6.55]). ConclusionsThere is scarce evidence to confirm an association between the IL-10 (−1082) polymorphism and the risk of ITP. However, the IL-10 (−1082) polymorphism might be associated with the risk of acute ITP. Additional large, well-designed epidemiological studies should be performed to draw definitive conclusions.

Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility.

BackgroundMultiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS.MethodsPubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS.ResultsA total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians.ConclusionFOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies.Level of evidenceLevel III diagnostic study.