ObjectiveTo investigate the relationship between the G196A and C270T polymorphism and epilepsy.MethodsDatabase including PubMed, EMbase, the Cochrane Library, CNKI and Wan fang data were retrieved upto September, 2017 to collect the case-control study concerning BDNF two polymorphisms G196A/C270T and epilepsy. Two reviewers independently screened the literature, extracted the data, and assessed the quality of methodology. Then Meta-analysis was performed using RevMan 5.2 software.Results①A total of 9 studies were included in the Meta-analysis between BDNF G196A and epilepsy. The studies included 1841 epilepsy patients and 6467 healthy control subjects. The G allele increase the risk of epilepsy[OR=1.13, 95%CI (1.06–1.21), P=0.0001]. When stratified by Asian and western subgroup, a similar trend of associated was detected with Asian epilepsy patients [OR=1.13, 95%CI (1.05–1.20), P=0.0004]. When stratified by epilepsy type, the G allele increase the risk of temporal lobe epilepsy [OR=1.18, 95%CI (1.04–1.34), P=0.008]. ② The Meta-analysis between BDNF C270T and epilepsy included 4 studies, 594 epilepsy patients and 738 healthy control subjects. The result suggested the frequency of the CT genotype and of the C270T T allele was not associated with epilepsy.ConclusionsBDNF G196A polymorphism is a susceptibility locus for temporal lobe epilepsy and Asian epilepsy patients.
Objective To investigate whether ADAM33 ( A disintegrin and metalloproteinase 33) gene polymorphismhas effect on the airway inflammation of COPD. Methods A total of 312 COPD patients were recruited for this study. Four polymorphic loci ( T2, T1, S2, and Q-1) of ADAM33 were selected for genotyping by using the polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) method. Total and differential cell counts, contents of TNF-α, IL-6, IL-8, and VEGF in induced sputumwere detected. The relationship between genotypes and inflammatory reaction was analyzed. Results On locus T2, the cell counts and content of TNF-αin induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.01 and Plt;0.05) . On locus T1, the lymphocyte counts in induced sputumincreased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.05) ; but the content of IL-8 in induced sputumwas higher in AA and AG genotypes ( Plt;0.05) . On locus Q-1, the contents of VEGF and IL-8 in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes (Plt;0.05) . On locus S2, the total cell counts in induced sputumincreased significantly in the carriers with GG genotype than those with CC and CG genotypes ( Plt;0.05) , and the content of IL-8 in induced sputum increased significantly in GG genotype ( Plt;0.01 ) . Conclusion These results suggest that ADAM33 polymorphism may participate the pathogenesis of COPD by promoting airway inflammation.
ObjectiveTo investigate the association between single nucleotide polymorphism (SNP) rs3754219 in the glucose transporters 1 (GLUT1) gene and genetic susceptibility to type 2 diabetes mellitus (T2DM) in Han population in Guangdong Province.MethodsA total of 1 092 T2DM patients (case group) and 1 092 healthy controls (control group) diagnosed or examined between November 2011 and October 2014 form 10 hospitals were enrolled in this study. SNPscanTM SNP classification technology was used to detect the polymorphism of rs3754219 of GLUT1 genetype. Finally, 1 067 T2DM patients and 1 054 healthy controls were included, removing 37 individuals with SNP typing deletion rates >20% and 26 individucals with failed SNP site genotyping. The differences in allele frequency distribution, genotype, and genetic models between the two groups were analyzed.ResultsAfter correction for age and body mass index, there was no statistically significant difference in allele frequency or polymorphism genotype frequency of rs3754219 (P>0.05). There was no statistically significant difference between the two groups under different genetic models (P>0.05).ConclusionGenetic susceptibility to T2DM in Han population in Guangdong Province may be unrelated to the GLUT1 rs3754219 SNP.
The association between single nucleotide polymorphism and disease is a typical representation of genetic association studies. Compared with the traditional dichotomous data, single nucleotide polymorphism data has its own characteristics, and 5 genetic models are commonly performed in meta-analysis. In this paper, we show how to use the " meta” package in R software to conduct meta-analysis of single nucleotide polymorphism research through examples.
Objective To explore the relationship between alcohol induced osteonecrosis of the femoral head (ONFH) and the single nucleotide polymorphisms (SNP) of methylene tetrahydrofolate reductase (MTHFR) 677 C/T. Methods From July 2005 to May 2008, eighty-nine male patients with alcohol induced ONFH were selected as the patient group, aged from 24 to58 years old (mean 44.3 years old). The time of drinking was about 17 years, 375 mL/day. The imaging evidence showed ONFH with no other history associated to ONFH. Seventy-seven male healthy adults were selected as the control group, aged from 23 to 52 years old (mean 42.7 years old). The time of drinking was about 14 years, 335 mL/day. The imaging evidence showed no ONFH. The 2 mL blood sample was acquired from every subject. DNA was purified from leucocyte at first, then was ampl icated by PCR, the product of PCR was sequenced at last. The SNP of MTHFR 677 C/T was analyzed with SPSS 12.0 software package. Results The TT genotype and T allele frequencies of MTHFR 677 C/T were 27.2% and 52.0% (P gt; 0.05) in the control group, and the distribution of genotype was consistent with Hardy-Weinberg equil ibrium. The genotype frequencies of CC, CT and TT were 23.4% (18 cases), 49.4% (38 cases) and 27.2% (21 cases) in the control group, were 14.6% (13 cases), 36.0% (32 cases) and 49.4% (44 cases) in the patient group; showing statistically significant differences (P lt; 0.05). The allele frequencies of C and T were 48.0% (74) and 52.0% (80) in the control group, and were 32.6% (58) and 67.4% (120) in the patient group; showing statistically significant differences (P lt; 0.05). The frequencies of C, T alleles and TT genotype were higher in the patient group than in the control group, showing statistically significant differences (P lt; 0.05). The odds ratios were 0.523, 1.914 and 2.607, respectively; the 95% confidence interval were 0.335-0.816, 1.226-2.987, 1.359-5.001, respectively. Conclusion The relationship may exist between the SNP of MTHFR 677 C/T and alcohol induced ONFH.
Objective To explore the causal relationship between gut microbiota and urinary tract infections (UTI) using data from genome-wide association studies. Methods The gut microbiota data were sourced from the MiBioGen consortium, comprising genetic variables from 18 340 individuals. UTI data (ieu-b-5.65) were derived from the UK Biobank. Six methods including inverse variance weighted (IVW), Mendelian randomization (MR)-Egger, maximum likelihood, simple mode, weighted mode, and weighted median were employed for two-sample MR analysis on these datasets. Additionally, MR-PRESSO was used to detect and correct for heterogeneity and outliers in the analysis. Cochran’s Q test and leave-one-out analysis were applied to assess potential heterogeneity and multiple effects. Furthermore, reverse MR analysis was conducted to investigate causal relationships between UTI and gut microbiota. Results According to IVW method analysis results, bacterial genera Eggerthella (OR=1.08, 95%CI 1.01 to 1.16, P=0.034) and Ruminococcaceae (UCG005) (OR=1.10, 95%CI 1.01 to 1.20, P=0.022) were found to increase the risk of UTI, while Defluviitaleaceae (UCG011) (OR=0.90, 95%CI 0.82 to 0.99, P=0.022) appeared to decrease it. Reverse MR analysis did not reveal a significant effect of UTI on these three bacterial genera. Our study found no evidence of heterogeneity or pleiotropy based on the results of Cochran’s Q test, MR-Egger, and MR-PRESSO global test. Conclusion In this MR study, we demonstrate a causal association between Eggerthella, Ruminococcaceae, Defluvitalaceae and the risk of urinary tract infections.
Objective To investigate the association between MDM2 gene promoter SNP 309 polymorphism and leukemia susceptibility. Methods Such databases as Ovid, EBSCO, PubMed, CNKI, CBM, VIP and WanFang Data were searched to collect the case-control studies published from January 1990 to June 2012. According to the inclusion and exclusion criteria, the studies were screened, the data were extracted, and the methodological quality of the included studies was evaluated. Then meta-analysis was conducted using RevMan 5.0 and Stata 10.0 software, the pooled odds ratio (ORs) with 95% confidence interval (CI) were calculated, and the sensitivity and publication bias were evaluated at the same time. Results A total of 9 studies within 8 articles were included, which involved 1 821 cases and 5 642 controls. The results of meta-analysis showed that, the susceptibility of leukemia was increased in the G allele carriers compared with the T allele carriers (OR=1.26, 95%CI 1.08 to 1.46, P=0.003), and the leukemia risk was higher in the GG genotype populations compared with the TT genotype populations (OR=1.46, 95%CI 1.02 to 2.10, P=0.04). Among Asians with recessive models, the leukemia risk was higher in the homozygous GG genotype compared with both the heterozygous GT genotype and the homozygous TT genotype (OR=2.00, 95%CI 1.37 to 2.92, P=0.000 3). There was no obvious publication bias. Conclusion MDM2 gene promoter SNP 309 polymorphism is associated with the susceptibility of leukemia, and the G allele is likely to be the risk factor for leukemia.
ObjectiveTo analyze the causal relationship between SARS-CoV-2 infection and retinal vascular obstruction by mendelian randomization (MR). MethodsA two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) in European populations was conducted. The GWAS data for SARS-CoV-2 infection comprised cases of common infection (2 597 856), hospitalized infection (2 095 324), and severe infection (1 086 211). Data on retinal vascular obstruction were obtained from the FinnGen database, which included 203 269 cases of retinal artery obstruction and 182 945 cases of retinal vein obstruction (RVO). Inverse variance weighting (IVW), random effects models, weighted median (WM), MR-Egger regression, simple models, and weighted models were used to analyze the bidirectional causal relationship between different SARS-CoV-2 infection phenotypes and retinal obstruction. The Q statistic was used to assess heterogeneity among single nucleotide polymorphisms (SNP), while MR-Presso was utilized to detect SNP outliers, and MR-Egger intercept tests were performed to evaluate horizontal pleiotropy. ResultsThe MR analysis, using IVW, random effects models, MR-Egger, WM, and weighted models, indicated no significant association between common SARS-CoV-2 infection, hospitalized infection, severe infection, and retinal vascular obstruction (P＞0.05). Additionally, retinal vascular obstruction did not show a significant association with the various SARS-CoV-2 infection phenotypes (P＞0.05). In the simple model, a significant association was found between severe SARS-CoV-2 infection and RVO (P＜0.05), as well as between RVO and common SARS-CoV-2 infection (P＜0.05). No heterogeneity was observed in the IVW and MR-Egger analyses (P＞0.05). The MR-Egger test provided no evidence of horizontal pleiotropy (P＞0.05), and MR-Presso detected no outlier SNP. ConclusionThe findings of this study do not support a causal relationship between SARS-CoV-2 infection and the occurrence of retinal vascular obstruction.
Objective To review the research progress of bone morphogenetic protein (BMP) and the liability of ossification of the posterior longitudinal ligament (OPLL). Methods Recent literature concerning BMP and the liability of OPLL was reviewed, analysed, and summarized. Results The single nucleotide polymorphisms (SNPs) of BMP gene may produce a minor cumulative effect and increase individual susceptibility to OPLL. A variety of environmental factors can promote the occurrence and development of OPLL by increasing the expression of BMP gene. Conclusion The SNPs of BMP gene may increase individual susceptibility to OPLL. However, interaction of cumulative effect of the SNPs and environmental factors can promote the liability to OPLL.
ObjectiveTo investigate the relationship between the gene polymorphism of autophagy-related gene 3 (ATG3) and the development and clinical symptoms of tuberculosis in tuberculosis patients in western China.MethodsAccording to the inclusion and exclusion criteria, 476 tuberculosis patients (tuberculosis group) who were admitted to West China Hospital of Sichuan University from December 2014 to November 2015 and 475 healthy controls (healthy control group) who underwent health examination during the same period were finally included. High-throughput genotyping technology was used to detect genotypes of three single nucleotide polymorphisms (SNPs) (rs2638029, rs2638037, rs3732817) of ATG3 gene, and relevant clinical data of subjects were collected. The relationship between gene polymorphism and susceptibility to tuberculosis and clinical symptoms was analyzed by statistical methods such as χ2 test and logistic regression model.ResultsExcept for GA genotype [odds ratio (OR) =1.375, 95% confidence interval (CI) (1.048, 1.805), P=0.022] and dominant genetic model GG+GA [OR=1.326, 95%CI (1.024, 1.717), P=0.032] in rs2638037, there was no statistically significant difference in the allele frequency, genotype and genetic patterns of rs2638029, rs3732817 and rs2638037 between the two groups (P>0.05), after the adjustment of the gender and age. But after correction by Bonferroni, GA genotype and dominant genetic patterns GG+GA showed no statistical significance between the two groups (P=0.132, 0.201). Haplotype CGA was associated with tuberculosis susceptibility [OR=1.262, 95%CI (1.001,1.593), P=0.048]. There was a statistically significant difference in weight loss symptoms among rs2638037 genotypes (χ2=8.131, P=0.017).ConclusionsThe haplotype CGA of three SNPs of ATG3 gene may be involved in the development of tuberculosis. The rs2638037 single nucleotide polymorphism may be related to weight loss, and more research is needed in the future.