Heterozygote Model Research Articles

Paraoxonase 1 gene (Q192R) polymorphism confers susceptibility to coronary artery disease in type 2 diabetes patients: Evidence from case-control studies.

Numerous published studies have investigated the relationship between the paraoxonase 1 (PON1) gene Q192R (rs662) polymorphism and the risk of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. However, the results are still conflicting and inconclusive. Potentially eligible articles were searched for in related databases. Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the associations. Subgroup analysis was performed based on ethnicity. Ten case-control studies were included. A significant increase in the susceptibility for CAD in T2DM patients was found in the allelic model (OR = 1.49, p < 0.001), homozygote model (OR = 2.47, p < 0.001), heterozygote model (OR = 1.47, p < 0.001), dominant model (OR = 1.64, p < 0.001), and recessive model (OR = 1.74, p = 0.001). In subgroup analysis by ethnicity, a significant increase susceptibility was found in Asian populations in the allelic model (OR = 1.39, p = 0.001), homozygote model (OR = 2.15, p = 0.002), heterozygote model (OR = 1.37, p = 0.006), recessive model (OR = 1.65, p = 0.012), and dominant model (OR = 1.54, p < 0.001). A similar significant increase in susceptibility was found in Caucasian populations in the allelic model (OR = 1.75, p = 0.002), homozygote model (OR = 3.39, p = 0.002), recessive model (OR = 1.98, p = 0.030), heterozygote model (OR = 1.64, p = 0.001), and dominant model (OR = 1.83, p < 0.001). The results suggest that the PON1 Q192R polymorphism is associated with a significantly increased risk of CAD in T2DM patients in both Asian and Caucasian populations.

Interleukin-8 Gene -251 A/T (rs4073) Polymorphism and Coronary Artery Disease Risk: A Meta-Analysis.

BackgroundInflammation plays an important role in the pathogenesis of coronary artery disease (CAD). Studies have reported that inflammatory cytokine interleukin-8 (IL-8) gene −251 A/T (rs4073) polymorphism is correlated with CAD susceptibility, but the result remains controversial. The objective of this study was to clarify the association between IL-8 gene −251 A/T polymorphism and CAD risk.Material/MethodsA meta-analysis included 8244 patients from 9 individual studies with 10 populations was conducted. Heterogeneity test was conducted, and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated used fixed-effect or random-effects model accordingly. Publication bias was evaluated with the Begg’s funnel plot and Egger’s test. Sensitivity analysis was also conducted.ResultsA significant association between IL-8 gene −251 A/T polymorphism and CAD risk was found in the dominant model (OR 1.42, 95% CI 1.16–1.76, P<0.001), recessive model (OR 1.30, 95% CI 1.12–1.52, P<0.001), allelic model (OR 1.28, 95% CI 1.12–1.47, P<0.001), homozygote model (OR 1.59, 95% CI 1.21–2.08, P<0.001), and heterozygote model (OR 1.35, 95% CI 1.11–1.64, P=0.002). Subgroup analysis by ethnicity found significant associations in the Chinese population in the dominant model(OR 1.43, 95% CI 1.26–1.61, P<0.001), recessive model (OR 1.39, 95% CI 1.21–1.59, P<0.001), allelic model (OR 1.31, 95% CI 1.21–1.42, P<0.001), homozygote model (OR 1.66, 95% CI 1.41–1.95, P<0.001), and heterozygote model (OR 1.34, 95% CI 1.18–1.52, P<0.001), but no significant association was found in the Caucasian population. No significant publication bias was found.ConclusionsThe IL-8 gene −251 A/T polymorphism was significantly associated with CAD risk in the Chinese population but not in the Caucasian population, −251 A allele carrier had an increased risk of CAD in the Chinese population.

Association of rs2234693 and rs9340799 polymorphisms of estrogen Receptor-1 gene with radiographic defined knee osteoarthritis: A meta-analysis

ObjectiveTo evaluate the association of ESR1 rs2234693 and rs9340799 polymorphisms with radiographic defined knee osteoarthritis (OA), a case-control and meta-analysis was performed. MethodsA total of 25 case-control studies with 7,144 cases and 8,468 controls with were included. ResultsThere was a significant association between rs2234693 polymorphism and radiographic knee OA under heterozygote model (CT vs. TT: OR = 1.164, 95% CI 1.053–1.286, p = 0.003). However, there was no association between rs9340799 and radiographic knee OA. In subgroup analysis by ethnicity, risk estimates were not augmented. ConclusionsOur results showed that the ESR1 rs2234693 polymorphism might be associated with radiographic defined knee OA, but not rs9340799.

The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians

Although published studies have reported the association between MTHFR C677T (rs 1801133), A1298C (rs 1801131), and MTRR A66G (rs1801394) polymorphisms and male infertility in Asian populations, the results are conflicting. In order to accurately evaluate the relevance, a meta-analysis was performed.We searched for potential studies in 4 databases, containing PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang database until May 31, 2018. The summarized odds ratio (OR) with 95% confidence intervals (95% CI) were calculated to evaluate the relevance in 5 genetic models. The heterogeneity test, sensitivity analysis, and publication bias test was performed by Review Manager 5.3 software.Overall, 22 case–control studies with 5049 cases and 4157 controls were included in this meta-analysis, which contained 20 studies of MTHFR C677T polymorphism, 12 studies of MTHFR A1298C polymorphism and 4 studies of MTRR A66G polymorphism. The results indicated that MTHFR C677T, A1298C, and MTRR A66G polymorphisms were significantly associated with male infertility in Asian populations (Dominant model: MTHFR CC + CT vs TT: OR = 0.60, 95% CI (0.53, 0.67), P <.00001; MTHFR AA + AC vs CC: OR = 0.62, 95% CI (0.49, 0.79), P = .0001; MTRR AA + AG vs GG: OR = 0.60, 95% CI (0.45, 0.81), P = .001. Recessive model: MTHFR CC vs CT + TT: OR = 0.67, 95% CI (0.61, 0.74), P <.00001; MTHFR AA vs AC + CC: OR = 0.79, 95% CI (0.70, 0.88), P <.0001; MTRR AA vs AG + GG: OR = 0.70, 95% CI (0.56, 0.88), P = .002. Heterozygote model: MTHFR CC vs CT: OR = 0.74, 95% CI (0.67, 0.82), P <.00001; MTHFR AA vs AC: OR = 0.83, 95% CI (0.73, 0.93), P = .002; MTRR AA vs AG: OR = 0.76, 95% CI (0.60, 0.92), P = .02. Homozygote model: MTHFR CC vs TT: OR = 0.48, 95% CI (0.41, 0.56), P <.00001; MTHFR AA vs CC: OR = 0.61, 95% CI (0.39, 0.93), P = .02; MTRR AA vs GG: OR = 0.51, 95% CI (0.36, 0.72), P = .0001. Allele model: MTHFR C vs T: OR = 0.70, 95% CI (0.66, 0.75), P <.00001; MTHFR A vsC: OR = 0.82, 95% CI (0.71, 0.95), P = .01; MTRR A vs G: OR = 0.76, 95% CI (0.66, 0.88), P = .00003). Stratified analyses by geographical location and source of controls showed the same results. Sensitivity analyses indicated that the final consequences of this meta-analysis were stable, and the publication biases test had not found obvious asymmetry.This meta-analysis indicates that MTHFR C677T, A1298C, and MTRR A66G polymorphisms are the risk factors with susceptibility to male infertility in Asians.

TLR2 Arg753Gln Gene Polymorphism Associated with Tuberculosis Susceptibility: An Updated Meta-Analysis

Objective To date, a series of studies were conducted to investigate the association between TLR2 (Toll-like receptor 2) Arg753Gln gene polymorphism and tuberculosis (TB). However, the results were inconsistent. This meta-analysis was performed to elucidate the roles of TLR2 Arg753Gln gene polymorphism in TB. Methods All available articles were searched from online databases such as PubMed, Medline, CNKI, and Wanfang. Statistical analyses were performed using the STATA12.0 (Stata Corp LP, College Station, TX, United States) software. Results 32 case-control studies comprising 5943 cases and 5991 controls were identified in this meta-analysis. Overall, the TLR2 Arg753Gln gene polymorphism was associated with high TB risk in allele model (A vs. G: OR=2.20, 95%CI=1.60-3.04, P≤0.01), dominant model (AA+AG vs. GG: OR=2.70, 95%CI=2.00-3.65, P≤0.01), and heterozygote model (AG vs. GG contrast: OR=2.97, 95%CI=2.39-3.69, P≤0.01). Subgroup analysis by ethnicity indicated that the A allele increased susceptibility to TB in Asian (OR=3.35, 95%CI=2.36-4.74) and Caucasian populations (OR=2.62, 95%CI=1.77-3.87), but not in African (2.08, 95%CI=0.62-2.72) or mixed populations (OR=0.76, 95%CI=0.36-1.14). Stratified analysis by sample type suggested that the A allele associated with high pulmonary tuberculosis (PTB) risks (OR=2.43, 95%CI=1.66-3.54), but not with extra pulmonary tuberculosis (EPTB) (OR=1.84, 95%CI=0.83-4.06). Conclusion this meta-analysis suggested the following: (1) TLR2 Arg753Gln polymorphism is significantly associated with high TB risk. (2) In subgroup analysis based on ethnicity, TLR2 Arg753Gln polymorphism elevates the risk of TB in Asian and Caucasian populations, but not in African or mixed populations. (3) Stratified by sample type, TLR2 Arg753Gln polymorphism is associated with increased PTB risk, but not with EPTB.

Non-syndromic cleft lip with or without palate susceptible loci is associated with tooth agenesis.

Non-syndromic tooth agenesis (NSTA) may share common genetic factors with non-syndromic cleft lip with or without cleft palate (NSCL/P). Single-nucleotide polymorphisms (SNPs) were associated with individual's susceptibility to these anomalies. We selected five NSCL/P-associated SNPs from our previous genome-wide association study (GWAS) to test for the associations with NSTA. A total of 677 NSTA cases and 1,144 healthy controls were recruited in this case-control study. Five genome-wide NSCL/P-associated SNPs (rs2235371, rs7078160, rs8049367, rs4791774, and rs13041247) were genotyped by TaqMan platform and evaluated for the associations with NSTA using plink software. No significant associations between these SNPs and risk of NSTA were observed in the overall analysis and subgroup analysis with the number of missing teeth. However, in the subgroup analysis by tooth position, rs8049367 was nominally associated with mandibular premolar agenesis (Dominant model: ORdom =0.66, 95% CIdom =0.47-0.93, pdom =0.016; Heterozygote model: ORhet =0.60, 95% CIhet =0.41-0.88, Phet =0.008). Rs4791774 showed a nominal association with congenitally missing maxillary canine (Dominant model: ORdom =0.53, 95% CIdom =0.28-0.98, pdom =0.041; Heterozygote model: ORhet =0.50, 95% CIhet =0.26-0.97, Phet =0.041) and premolar (Additive model: OR=0.59, 95% CI=0.36-0.96, p=0.035). This study showed that NSCL/P susceptible loci rs8049367 and rs4791774 were probably associated with the risk of NSTA.

Association of PTTG1 polymorphism rs1895320, rs2910200 and rs6882742 with non-functioning pituitary adenomas in Chinese Han population: a case-control study.

Due to absence of clinical manifestations of hormonal hyper secretion, the treatment of Nonfunctioning pituitary adenoma (NFPA) was always delayed. PTTG1 was reported to be overexpressed in most of pituitary tumors, however, the polymorphism of PTTG1 rs1895320, rs2910200 and rs6882742 with NFPA were still not fully elucidated in NFPA. Thus, a hospital based case control study which included 79 patients and 142 healthy control participants were conducted. DNA was extracted from peripheral blood samples and genotyped by Mass Array methods. In addition, a meta-analysis of rs2910200 was also employed to further testify the conclusion. Significant difference were observed between patients and healthy controls under rs2910200 locus between allelic genotype (p = 0.0219). However, no other significant difference was observed in rs1895329 and rs6882742. In addition, a logistic regression analysis showed that the dominant model of rs2910200 were closely correlated with the NFPA susceptibility (OR = 1.951, 95% CI:1.075-3.542, p = 0.028). While no significant difference was observed in the rs1895320 and rs6882742 under dominant model, recessive model and additive model The meta-analysis results showed that the dominant model and heterozygote model can significantly increase the risk of PA (p = 0.007, OR = 1.57, 95% CI:1.14-2.18; p = 0.009, OR = 1.57, 95% CI:1.12-2.19). Whereas no significant difference were observed under the homozygous model and recessive model. In conclusion, the polymorphism of PTTG1 rs2910200 dominant model and T allelic might increase the risk of NFPA.

ASSOCIATION OF INTERLEUKIN-10 -592A>C AND -819T>C POLYMORPHISMS WITH GASTRIC CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 44 CASE-CONTROL STUDIES.

ABSTRACTIntroduction:A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive. Objective:To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis. Method:An electronic search was performed of several databases to identify relevant studies up to April 2018. Results:A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C. Conclusion:The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.

Association between TNF-ɑ-308G/A polymorphism and esophageal cancer risk: An updated meta-analysis and trial sequential analysis.

Background: TNF-α-308G/A (rs1800629) polymorphism has been previously implicated in the susceptibility to esophageal cancer, but results of these studies remained controversial or ambiguous. A meta-analysis was conducted to provide a more reliable conclusion about the association between TNF-ɑ-308G/A polymorphism and risk of esophageal cancer.Methods: Databases such as PubMed, EMBASE, Web of Science and CNKI were searched for relevant articles published till June 1, 2018. We used the pooled odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Subgroup analysis was carried out according to ethnicity, source of controls and genotyping method. A trial sequential analysis (TSA) was performed to reduce the risk of type I error and evaluate whether the results of our meta-analysis were credible.Results: A total of 9 published case-control studies with 1,435 esophageal cancer patients and 3,762 healthy controls were identified. Overall, our results indicated no significant correlation between TNF-α-308G/A polymorphism and increased risk of esophageal cancer in the fixed-effects model (allele model: pooled OR=1.11, 95% CI: 0.96-1.27, homozygote model: pooled OR=1.23, 95% CI: 0.77-1.95, heterozygote model: pooled OR=1.14, 95% CI: 0.97-1.35, dominant model: pooled OR=1.14, 95% CI: 0.97-1.34 and recessive model: pooled OR=1.00, 95% CI: 0.64-1.56). Subgroup analysis by ethnicity, source of controls and genotyping method showed no significant increase in the risk of esophageal cancer. TSA results need further investigation with a large sample size to certify such association.Conclusions: This meta-analysis study suggested no significant association between TNF-ɑ-308G/A polymorphism and the risk of esophageal cancer.

Gene polymorphism associated with endothelial nitric oxide synthase (4VNTR, G894T, C786T) and unexplained recurrent spontaneous abortion risk: A meta-analysis.

To evaluate the association between endothelial nitric oxide synthase gene polymorphisms (4VNTR A/B, G894T, C786T) and risk of URSA.Related case-control studies were collected by computers. A meta-analysis was conducted using Stata 12.0 software to assess the strength of association.Altogether 37 articles were examining the relationship between endothelial nitric oxide synthase gene polymorphisms and URSA, among which sixteen (16) studies were related to 4VNTR, twelve (12) to G894T, and nine (9) to C786T, the study suggested that 4VNTR A/B polymorphism was closely connected with URSA risk under all gene models except for recessive model (AA vs. BB + AB). The integrated result which indicated the association between G894T gene mutation and URSA risk had been shown under homozygote (TT vs. GG; OR 1.585, 95%CI 1.175–2.138) and recessive models (TT vs. TG + GG; OR 1.530, 95%CI 1.142–2.052). Considering heterogeneity in the remaining gene models, subgroup analysis was performed on ethnicity, and the results showed that it was the dominant (TT + TG vs. GG; OR 1.585, 95%CI 1.175–2.138) and additive models (T vs. G; OR 1.727, 95%CI 1.372–2.175) of G894T in Asians and the heterozygote model (TG vs. GG; OR 1.015, 95%CI 0.846–1.217) in Caucasians that were associated with URSA (P < .05). Besides C786T gene was significantly connected with URSA under all models except for additive model (T vs. C).It is of great guiding significance for screening out and preventing URSA among high-risk women via testing on 4VNTR A/B, G894T, C786T eNOS under gene models mentioned above which are closely associated with URSA.

ASSOCIATION BETWEEN SINGLE NUCLEOTIDE POLYMORPHISM RS4919510 (C&gt;G) IN MIRNA-608 AND BREAST CANCER IN VIETNAMESE POPULATION

Breast cancer (BC) is a complex disease throughout the world and it is one of the most common cancer among women both in developed and developing countries. To enhance the survival of BC patients, genetic factors are used for early diagnosis because they are non-changed factors and present ability of cells to proliferate and metastasize. MiR-608 targets many genes which are vital for development, differentiation, motility, apoptosis and angiogenesis. The SNP rs4919510 (C/G) affects the processing of the pre-miRNA to its mature form and the ability to regulate target genes. This SNP has been demonstrated to relate to breast cancer in Chinese and Iranian population. Our study aimed to investigate the association between the SNP rs4919510 and BC in Vietnamese population. 106 cases and 101 controls were genotyped using optimized tetra-ARMs-PCR method, then statistical analysis was applied to examine the correlation of the SNP. The results show that this SNP is high polymorphism with the frequencies of minor allele C is 24.8% and major allele G is 75.2% in Vietnamese population. Statistic result revealed an obvious increased risk of BC among Vietnamese women when compared of heterozygote model and dominant model (CG vs. GG: OR=1.93, 95% CI: 1.09-3.45, p= 0.02; CC+CG vs. GG: OR=1.83, 95%CI: 1.05-3.17, p=0.03). Our study suggested that the polymorphism of rs4919510 may be associated with BC risk in Vietnamese individuals.

Urotensin-II gene rs228648 polymorphism associated with the risk of diabetes mellitus.

Background: Urotensin-II (UII) rs228648 polymorphism has been reported to be associated with the risk of diabetes mellitus (DM) with inconsistent results. The present study sought to reassess the relationship between this polymorphism and susceptibility to DM by meta-analysis.Methods: Relevant eligible studies and whole genome association study (GWAS) data electronically searched were pooled to evaluate the strength of the association with odds ratios (ORs) and 95% confidence intervals (CIs).Results: Seven case–control studies involving 894 cases and 1186 controls were finally included in the meta-analysis. Overall analyses indicated that UII gene rs228648 variant was significantly associated with reduced risk of DM (allele, A vs. G: OR = 0.68, 95%CI = 0.56–0.82; dominant, AA+GA vs. GG: OR = 0.70, 95%CI = 0.53–0.91; homozygote, AA vs. GG: OR = 0.41, 95%CI = 0.28–0.61; recessive, AA vs. GA+GG: OR = 0.36, 95%CI = 0.19–0.71). In subgroup analyses based on ethnicity, the results showed a significant association of rs228648 polymorphism with decreased risk of DM in Chinese population under all five genetic models as well as in non-Chinese population under heterozygote and recessive models. Stratified analyses by specific type of DM also presented a significant association for common diabetes mellitus (CDM) under allele and homozygote as well as gestational diabetes mellitus (GDM) under all genetic models except for homozygote model. However, the synthetic analysis with GWAS data suggested an increased risk of DM with rs228648 effect allele in European population (OR = 1.01, 95%CI = 1.00–1.02).Conclusion: The present meta-analysis preliminarily suggested a potentially opposite role of rs228648 polymorphism associated with DM risk in the Chinese and European population. Further studies are in great request to verify the results.

The association between IGF1 Gene 3'-UTR polymorphisms and cancer risk: A Meta-analysis.

Insulin-like growth factor 1 (IGF1) gene three prime untranslated region (3'-UTR) polymorphisms have been reported to be associated with cancer risk. However, the conclusions of the relevant studies are not consistent. The present meta-analysis evaluates the relationship between IGF1 gene 3'-UTR polymorphisms (rs5742714, rs6214, and rs6220) and cancer risk. Articles regarding the relationship between IGF1 rs5742714, rs6214, and rs6220 polymorphisms and cancer risk were selected by searching the PubMed, Embase, and Web of Science databases before April 30, 2018. Altogether, we obtained 34 case-controlled studies from 20 articles, including 21,568 cases and 31,199 controls. The strength of associations was quantified using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). In the present meta-analysis, no significant associations were detected between rs5742714, rs6214, and rs6220 and overall cancer risk. Thus, in stratified analyses, we found that rs6214 was associated with a significantly reduced risk of breast cancer under the allele, heterozygote, and dominant models (A vs G: OR, 0.94, 95% CI,0.88-1.00, P = .044; GA vs GG: OR, 0.88, 95% CI, 0.80-0.97, P = .012; AA + GA vs GG: OR, 0.89, 95% CI, 0.81-0.97, P = .011), as well as pancreatic cancer under the recessive model (AA vs GA + GG: OR, 0.68, 95% CI,0.53-0.87, P = .003). Also, rs6220 was associated with a significantly increased risk of breast cancer under the homozygote model (GG vs AA: OR, 1.23, 95% CI, 1.02-1.48, P = .031). In addition, rs6220 was found to increase overall cancer risk among Caucasians under the allele model (G vs A: OR, 1.06, 95% CI, 1.00-1.13, P = .043). In this meta-analysis, we investigated and reviewed the relationship between IGF1 gene 3'-UTR polymorphisms (rs5742714, rs6214, and rs6220) and cancer risk based on present epidemiological studies. Further studies are needed to draw more precise conclusions in the future.

Association of PSEN1 rs165932 polymorphism with Alzheimer's disease susceptibility: An extensive meta-analysis

BackgroundMutations in the PSEN1 gene were found to be a causative factor with familial EOAD and PSEN1 genetic variations have the ability to alter APP metabolism. Numerous epidemiological, case-control studies have been conducted to identify the risk association between PSEN1 gene polymorphisms and Alzheimer's disease susceptibility. However, these results remain controversial. MethodsA systematic meta-analysis was performed based on previously published (Thirty seven) studies involving 12,059 participants to determine the association of rs165932 polymorphism with AD by calculating their pooled odds ratio and 95% confidence intervals under allelic, homozygote, heterozygote, dominant and recessive genetic models. Further, the publication bias was assessed by Begg's funnel plot, Egger's linear regression test and to measure the robustness of our meta-analysis, sensitivity test based on Leave one out method was also performed. Results: The analysis of rs165932 (G/T) polymorphism showed no significant association with AD risk in Caucasian, Asian and mixed ethnic populations under five genetic models. Overall, the meta-analysis demonstrated that rs165932 intronic polymorphism do not contribute to Alzheimer's disease susceptibility. ConclusionsLarge-scale case-control studies from multiple ethnic populations are needed for better understanding of PSEN1 gene polymorphisms in disease pathogenesis.

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism is Associated with Breast Cancer Risk: A Meta-Analysis

Background:A number of case-control studies were conducted to investigate the association of angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism with breast cancer. But the results remain controversial. This meta-analysis aims to comprehensively evaluate the association of ACE I/D polymorphism with breast cancer.Method:A comprehensive literature search on PubMed, Google Scholar, SCOPUS and ISI Web of Knowledge databases for studies published up to June 01, 2018 was performed. Summary odds ratios (ORs) and 95% confidence intervals (CI) were estimated. Publication bias of literatures was evaluated using funnel plots and Egger’s test.Results:A total of 20 studies including 2846 breast cancer cases 9299 controls meeting the predefined criteria were involved in the meta-analysis. Overall, the ACE I/D polymorphisms was significantly associated with breast cancer under the allele model (I vs. D: OR= 0.803, 95% CI 0.647-0.996, p=0.046), the homozygote model (II vs. DD: OR= 0.662, 95% CI 0.462-0.947, p=0.024), the heterozygote model (ID vs. DD: OR= 0.707, 95% CI 0.528-0.946, p=0.020), the dominant model (II+ID vs. DD: OR= 0.691, 95% CI 0.507-0.941, p=0.019). In the subgroup analysis by ethnicity, a significant association was found among Asian and Caucasian populations, but not among mixed populations.Conclusions:This meta-analysis suggests that ACE I/D polymorphism may be associated with increased risk of breast cancer, especially among Asian and Caucasians. However, well-designed studies with larger sample size and more ethnic groups are needed to further validate the results.

Genetic Relationship Between IL-6 rs1800796 Polymorphism and Susceptibility to Periodontitis

ABSTRACTBackground: There are accumulating reports for the potential role of Interleukin-6 (IL-6) rs1800796 polymorphism in the risk of periodontitis. However, distinct conclusions are observed. In this study, we have an interest in comprehensively analyzing the genetic relationship between IL-6 rs1800796 and the susceptibility to periodontitis.Methods: We retrieved the eligible case-control studies from on-line database and conducted a meta-analysis. P-value of association test, OR (odd ratios) and 95% CI (confidence interval) were calculated for the assessment of potential genetic association.Results: We enrolled a total of 20 case-control studies for pooling analysis. A positive association between periodontitis cases and controls was observed in the overall meta-analysis under all genetic models (all P < 0.05, OR > 1). Similar results were detected in the “population-based, PB” and “China” subgroups (all P < 0.05, OR > 1). In the “Asian” subgroup, there is an increased periodontitis risk under the allele, homozygote, heterozygote, dominant and carrier models (all P < 0.05, OR > 1). Nevertheless, negative results were found in the “Caucasian” subgroup under all models [all P > 0.05]. In addition, a positive association between IL-6 rs1800796 and the risk of chronic periodontitis was detected under the models of allele [G vs. C], GG vs. CC, GG vs. CC+ CG and carrier [G vs. C] (all P < 0.05, OR > 1).Conclusion: IL-6 rs1800796 may serve as one genetic risk factor for periodontitis patients in the Asian population, especially the Chinese population. G/G genotype of IL-6 rs1800796 appears to be associated with an increased risk of chronic periodontitis.

Association of MMP-8 rs2012390 and rs11225394 polymorphisms with osteonecrosis of the femoral head risks: Evidence from a meta-analysis.

Background:The association of MMP-8 rs2012390 and rs11225394 polymorphisms with osteonecrosis of the femoral head (ONFH) risks was investigated in several studies with conflicting results. We performed the meta-analysis to evaluate the association between them.Methods:Potentially relevant literatures were searched from the electronic databases of PubMed, Web of Science, and Cochrane Library. All databases were searched up to May 6, 2018. The strength of associations of the MMP-8 rs2012390 and rs11225394 polymorphisms with ONFH risk was assessed by crude odds ratios (ORs) with their 95% confidence intervals (CIs) under different genetic models.Results:A total of 1469 cases diagnosed with ONFH and 1211 healthy controls were included in the current meta-analysis. A remarkable association between rs11225394 in the MMP-8 gene and an increased risk of ONFH was found (allele model: OR = 1.33, 95% CI = 1.09–1.61, P = .005; heterozygote model: OR = 1.39, 95% CI = 1.13–1.71, P = .002; dominant model: OR = 1.40, 95% CI = 1.14–1.73, P = .002, respectively). Meanwhile, a significant association between MMP-8 rs2012390 and the decreased risk of ONFH was found in heterozygote model (OR = 0.63, 95% CI = 0.51–0.77, P < .00001).Conclusion:The meta-analysis results showed a remarkable association between rs11225394 in MMP-8 gene and an increased risk of ONFH and a significant association between MMP-8 rs2012390 and the decreased risk of ONFH.

Analysis of the Association of Polymorphisms rs5743708 in TLR2 and rs4986790 in TLR4 with Atopic Dermatitis Risk

ABSTRACTBackground: We carried out a meta-analysis to assess whether Toll-like receptor 2 (TLR2) rs5743708 and Toll-like receptor 4 (TLR4) rs4986790 polymorphisms are associated with the risk of atopic dermatitis.Methods: A systematic search of PubMed, Embase, and Web of Science was performed to identify eligible case–control studies on the association of rs5743708 and rs4986790 with the risk of atopic dermatitis. Statistical analyses of the odds ratio (OR), 95% confidence interval (CI), and p value were performed using STATA software.Results: Our meta-analysis included a total of nine case–control studies, all involving Caucasian populations. With respect to the TLR2 rs5743708 G/A polymorphism, there was a statistically significant difference in the overall risk of atopic dermatitis between the case and control groups [OR = 2.07, p value of association test, p(association) = 0.001 in allele (A vs. G) model; OR = 1.93, p(association) = 0.004 in carrier (A vs. G) model; OR = 2.07, p(association) = 0.001 in heterozygote (GA vs. GG) model; OR = 1.99, p(association) = 0.001 in dominant (GA+ AA vs. GG) model]. Similar positive results were observed in the subgroup analysis of “population-based control.” For the TLR4 rs4986790 A/G polymorphism, an increased atopic dermatitis risk was detected in the case group under the allele [OR = 1.78, p(association) = 0.013], carrier [OR = 1.69, p(association) = 0.027] and heterozygote [OR = 1.74, p(association) = 0.020] models, but not the dominant [OR = 1.44, p(association) = 0.070] model, in comparison to the population-based control group.Conclusion: Our meta-analysis revealed a novel finding that the heterogeneous “GA” genotype of the TLR2 rs5743708 and “AG” genotype of the TLR4 rs4986790 may be associated with increased susceptibility to atopic dermatitis in Caucasians.

Association Between Complement Factor C2/C3/CFB/CFH Polymorphisms and Age-Related Macular Degeneration: A Meta-Analysis.

Several previous studies have assessed the contribution of polymorphisms in genes encoding the complement factors C2/C3/CFB/CFH with the risk of age-related macular degeneration (AMD), however the results have been inconsistent. We conducted a meta-analysis to systematically review the potential association between complement factor polymorphisms and AMD. Studies that investigated associations between C2 (rs547154 and rs9332739), C3 (rs1047286), CFB (rs4151667 and rs641153), and CFH (rs551397 and rs2274700) polymorphisms and AMD were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Library databases for articles published prior to January 1, 2018. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate the association between these polymorphisms and AMD using Stata 12.0 software. Q and I2 statistics were used to evaluate between-study heterogeneity. Publication bias analyses were conducted using Begg's test. We also conducted an ethnic subgroup analysis. A total of 53 studies that included data for 53,774 patients and 56,973 healthy controls were evaluated. The pooled ORs for rs551397, rs2274700, rs4151667, rs641153, rs1047286, rs9332739, and rs547154 in the heterozygote model were 0.53 (95% CI: 0.45-0.61), 0.53 (95% CI: 0.40-0.70), 0.54 (95% CI: 0.46-0.63), 0.48 (95% CI: 0.4-0.57), 1.42 (95% CI: 1.22-1.66), 0.5 (95% CI: 0.45-0.56), and 0.52 (95% CI: 0.43-0.62), respectively. Our findings from this analysis confirmed the protective role of C2/CFB/CFH polymorphisms in the development of AMD, but showed that the single nucleotide polymorphism in C3 was a high-risk factor for AMD. The racial analysis results suggested that the effect of variant alleles was stronger in Caucasians than Asians.

Association of miRNA-146a rs2910164 and miRNA-196 rs11614913 polymorphisms in patients with ulcerative colitis

Background:It has been reported that the single nucleotide polymorphisms (SNPs) miRNA-196 (miR-196) rs11614913 and miRNA-146a (miR-146a) rs2910164 are related to susceptibility to ulcerative colitis (UC). Because the previously reported results have been mixed and uncertain, the aim of this study was to perform a meta-analysis and review to assess the relationship between these 2 SNPs and UC risk.Methods:In this analysis, 5 studies involving 1023 cases and 1769 controls for miR-196 rs11614913 and 4 studies involving 827 cases and 1451 controls for miR-146 rs2910164 were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size.Results:A decreased risk of UC was identified in homozygote comparison (GG vs CC: OR = 0.69, 95% CI: 0.52–0.93, P = .02), recessive comparison (GG vs CG + CC: OR = 0.74, 95% CI: 0.59–0.92, P = .007), and dominant comparison (GG + CG vs CC: OR = 0.79, 95% CI: 0.65–0.97, P = .02) of miR-146 rs2910164 in Asian but not Caucasian population. No evidence of an association was shown between the rs11614913 polymorphism and UC risk in allelic, heterozygote, homozygote, recessive, and dominant models in both Caucasian and Asian populations (P > .05).Conclusions:MiR-146 rs2910164, but not miR-196 rs11614913, was associated with a decreased risk of UC in Asian population. However, the results should be treated with caution because of the limited sample size and heterogeneity. Well-designed studies with large sample sizes and more ethnic groups are needed to validate the risks identified in the current meta-analysis and review.