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Lung Dec 2015Several recent studies have provided evidence that polymorphisms in the interleukin-1 (IL1) gene are implicated in tuberculosis (TB). However, results of different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several recent studies have provided evidence that polymorphisms in the interleukin-1 (IL1) gene are implicated in tuberculosis (TB). However, results of different studies are inconsistent. The aim of this study was to perform a meta-analysis investigating the association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk.
METHODS
A systematic review of the English literature was conducted by searching Pubmed, Scopus, and ISI Web of Knowledge databases for relevant studies. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated using fixed effects models. Between-study heterogeneity and publication bias were also evaluated.
RESULTS
Nine case-control studies including 3327 participants were reviewed and analyzed. Our results did not indicate any association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk in the overall populations. The pooled OR of the IL1B -511 polymorphism was 1.09 (95 % CI 0.87-1.36) for the dominant model, 1.11 (0.89-1.38) for the recessive model, 1.15 (0.87-1.50) for the homozygote model, and 1.07 (0.94-1.23) for the allelic comparison model. ORs for the IL1B +3954 and IL1RN VNTR polymorphisms were similar. In subgroup analysis stratified by ethnicity, the results revealed no association between these polymorphisms and TB risk in black people, Asians, and Caucasians, respectively. We did not identify significant between-study heterogeneity across all studies, and there was no evidence of publication bias.
CONCLUSIONS
Our results indicate there is a lack of association between the IL1B (-511 and +3954), IL1RN VNTR polymorphisms and TB risk.
Topics: Alleles; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Minisatellite Repeats; Odds Ratio; Polymorphism, Genetic; Tuberculosis
PubMed: 26330006
DOI: 10.1007/s00408-015-9796-5 -
Molecular Psychiatry May 2004Large differences in clinical response to selective serotonin reuptake inhibitors (SSRIs) are observed in depressive patients with different genotypes. Quantification of... (Review)
Review
Large differences in clinical response to selective serotonin reuptake inhibitors (SSRIs) are observed in depressive patients with different genotypes. Quantification of these differences is needed to decide if genetic testing prior to antidepressant treatment is useful. We conducted a systematic review of the literature on the influence of polymorphisms in the serotonin transporter gene (SERTPR (or 5-HTTLPR) and STin2) on SSRI response. Studies were identified by the use of MEDLINE, EmBase and PsycINFO, references of articles, reviews and information from pharmaceutical companies. Nine studies assessing the influence of SERTPR or STin2 on treatment response were included. Outcome was expressed as the percentage of decrease in depression score (HAM-D or MADRS) or as the percentage of responders (> or =50% reduction on the depression scale). Both study methodologies and study outcomes showed large heterogeneity. Weighted mean decreases in depression score for patients with the s/s, s/l and l/l genotypes were 35.4, 46.3 and 48.0% at week 4, respectively, and 53.9, 54.6 and 48.3% at week 6. Among Caucasian patients, both mean decrease in depression score and response rate were lowest in the s/s group, while among Asian patients, results were inconsistent. Weighted response rates were 36.1% for the 10/12 genotype of the STin2 polymorphism and 80.7% for the 12/12 genotype (chi2=27.8, P<0.001) (only Asians). The available evidence points to a less favourable response to SSRI treatment among Caucasian patients with the SERTPR s/s genotype and among (Asian) patients with the STin2 10/12 genotype. In view of the scarcity and heterogeneity of the studies, however, current information is insufficiently reliable as a basis for implementing genetic testing in the diagnostic work-up of the depressive patient.
Topics: Adult; Asian People; Depressive Disorder; Drug Resistance; Female; Genotype; Humans; Introns; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Minisatellite Repeats; Nerve Tissue Proteins; Polymorphism, Genetic; Promoter Regions, Genetic; Serotonin; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; White People
PubMed: 15037864
DOI: 10.1038/sj.mp.4001488 -
Scandinavian Cardiovascular Journal :... Feb 2019Nitric oxide (NO) represents the most powerful endogenous molecule with vasodilator action mainly produced by endothelial nitric oxide synthase (eNOS) enzyme....
OBJECTIVES
Nitric oxide (NO) represents the most powerful endogenous molecule with vasodilator action mainly produced by endothelial nitric oxide synthase (eNOS) enzyme. Polymorphisms and epigenetic-sensitive mechanisms can modulate the expression of eNOS gene, leading to the endothelial dysfunction. This review updates on the mechanistic role of NO in the regulation of platelet activation, as well as the impact of eNOS genetic and epigenetic modifications on arterial thrombosis onset.
DESIGN
A systematic search was addressed to examination of PubMed databases with the following terms: nitric oxide; arterial thrombosis; endothelial dysfunction; DNA variations; epigenetic modifications; personalized therapy; network medicine.
RESULTS
G894T, -786T/C, and 4b/4a variable number tandem repeat (VNTR), are the main classes of polymorphisms harbored in eNOS gene associated to increased arterial thrombosis risk. DNA methylation, histone/non-histone modifications, and microRNA (miRNAs) can modulate eNOS gene expression. Investigators largely focused on the role of miRNAs in modulating NO production in arterial thrombosis development. In detail, miR-195, and miR-582 are inversely correlated both to eNOS and NO levels, thus suggesting novel biomarkers.
CONCLUSION
We are far from incorporating omics pathogenic data from bench to arterial thrombosis bedside. Network medicine is an emerging paradigm that ideally overcomes the current shortcomings of the reductionist approach. Despite several clinical limitations, the network-based analysis of the interactome might reveal the key nodes underlying the perturbations of the arterial thrombosis, thus advancing personalized therapy.
Topics: Animals; Arterial Occlusive Diseases; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Minisatellite Repeats; Nitric Oxide; Nitric Oxide Synthase Type III; Phenotype; Platelet Activation; Polymorphism, Genetic; Risk Factors; Thrombosis; Vasodilation
PubMed: 30741027
DOI: 10.1080/14017431.2019.1581943 -
BMJ Open Jan 2015To systematically review the evidence for the impact of study design and setting on the interpretation of tuberculosis (TB) transmission using clustering derived from... (Review)
Review
Effect of study design and setting on tuberculosis clustering estimates using Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR): a systematic review.
OBJECTIVES
To systematically review the evidence for the impact of study design and setting on the interpretation of tuberculosis (TB) transmission using clustering derived from Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) strain typing.
DATA SOURCES
MEDLINE, EMBASE, CINHAL, Web of Science and Scopus were searched for articles published before 21st October 2014.
REVIEW METHODS
Studies in humans that reported the proportion of clustering of TB isolates by MIRU-VNTR were included in the analysis. Univariable meta-regression analyses were conducted to assess the influence of study design and setting on the proportion of clustering.
RESULTS
The search identified 27 eligible articles reporting clustering between 0% and 63%. The number of MIRU-VNTR loci typed, requiring consent to type patient isolates (as a proxy for sampling fraction), the TB incidence and the maximum cluster size explained 14%, 14%, 27% and 48% of between-study variation, respectively, and had a significant association with the proportion of clustering.
CONCLUSIONS
Although MIRU-VNTR typing is being adopted worldwide there is a paucity of data on how study design and setting may influence estimates of clustering. We have highlighted study design variables for consideration in the design and interpretation of future studies.
Topics: Bacterial Typing Techniques; Cluster Analysis; Humans; Interspersed Repetitive Sequences; Minisatellite Repeats; Molecular Epidemiology; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length; Reproducibility of Results; Research Design; Tuberculosis
PubMed: 25609667
DOI: 10.1136/bmjopen-2014-005636 -
International Journal of Legal Medicine Jul 2021The etiology of sudden infant death syndrome (SIDS) remains an unsolved problem. The aim of this meta-analysis is to investigate the potential association between... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The etiology of sudden infant death syndrome (SIDS) remains an unsolved problem. The aim of this meta-analysis is to investigate the potential association between monoamine oxidase A (MAOA) promoter variable number tandem repeat (VNTR) polymorphism and SIDS risk.
METHODS
A systematic review and meta-analysis were conducted on studies from accessible electronic databases. Each VNTR variant was examined in each gender independently by comparing with the pooled results of other alleles.
RESULTS
A total of six independent case-control studies including 1022 SIDS cases and 1839 controls were enrolled in this meta-analysis. In both of the whole populations and Caucasian populations, male infants with the low-MAOA-expression alleles (2R+3R) were found to exhibit a statistically significant increased risk of SIDS, whereas those with a 4R allele exhibited a reduced risk of SIDS. Besides, an increased risk of SIDS was detected in male Caucasian infants with 2R or 3R alleles. However, none of the allele or genotype variants was associated with SIDS in female victims.
CONCLUSION
In male Caucasian infants, the low expression of MAOA promoter VNTR alleles (2R and 3R) is associated with an increased risk of SIDS, and the existence of the 4R allele could be regarded as a protective factor.
Topics: Alleles; Case-Control Studies; Female; Genotype; Humans; Infant; Male; Minisatellite Repeats; Monoamine Oxidase; Polymorphism, Genetic; Promoter Regions, Genetic; Sudden Infant Death; White People
PubMed: 33523250
DOI: 10.1007/s00414-020-02496-6 -
Molecular Biology Reports Dec 2012There seems to be a role for serotoninergic neuro-transmission in the pathophysiology of the epilepsies. Different groups have studied the role of regulatory variants in... (Meta-Analysis)
Meta-Analysis
There seems to be a role for serotoninergic neuro-transmission in the pathophysiology of the epilepsies. Different groups have studied the role of regulatory variants in the SLC6A4 gene, which code for the central serotonin transporter, in the complex genetics of temporal lobe epilepsy (TLE) obtaining contradictory findings. Therefore, a systematic review and critical analysis of this topic seem to be timely. Published studies up to October 2011 of TLE and the SLC6A4 promoter and intron 2 variant number repeat polymorphisms (VNTR) were identified by searches of Medline, Scopus and ISI-Web of Sciences databases. Meta-analysis of TLE case-control data were performed to assess the association of SLC6A4 VNTRs with TLE susceptibility. Pooled odds ratios were estimated by means of a genetic-model-free approach. The quality of the included studies was assessed by a score. The studies included compared a total of 991 TLE cases and 1,202 controls. We did not find synthetic evidence of association between SLC6A4 promoter and intron 2 variants and the risk of TLE. However, the intron 2 VNTR seems to have opposite effects in different populations. In this meta-analysis our findings were inconclusive in order to associate any of the 5-HT receptor gene variants with the risk of TLE.
Topics: Case-Control Studies; Epilepsy, Temporal Lobe; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Minisatellite Repeats; Odds Ratio; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 23065262
DOI: 10.1007/s11033-012-1949-5 -
Addiction Biology May 2020Genetics account for moderate variation of individual differences in developing alcohol use disorder (AUD), but it is unclear which genetic variations contribute to AUD... (Meta-Analysis)
Meta-Analysis
Genetics account for moderate variation of individual differences in developing alcohol use disorder (AUD), but it is unclear which genetic variations contribute to AUD risk. One candidate gene investigated due to its association with AUD is the dopamine D4 receptor gene (DRD4), which contains a 48-base pair variable number tandem repeat (VNTR) in exon 3 of its coding region. To date, no quantitative synthesis of the published literature on the effects of DRD4 VNTR variation on alcohol-related phenotypes has been conducted. MEDLINE, Embase, Web of Science, and PsycInfo were searched for studies that reported on alcohol craving, alcohol consumption, severity of AUD, and case-control (AUD versus no diagnosis of AUD) studies in DRD4L (seven repeats or more) carriers compared with DRD4S (six repeats or less) homozygotes. Random-effects meta-analysis was used for all analyses. A pooled sample size of 655 to 13,360 of 28 studies were included. Compared with DRD4S homozygotes, DRD4L carriers had increased number of drinking days (SMD: 0.205; 95% CI: 0.008 to 0.402), binge drinking days (SMD: 0.217; 95% CI: 0.0532 to 0.380), and severity of AUD (SMD: 0.143; 95% CI: 0.028 to 0.259). There was no difference between DRD4 VNTR genotypes on drinks per drinking day, largest number of drinks per day/occasion, and case-control analysis. It was not possible to conduct a meta-analysis of the craving data, but a systematic review of this literature found mixed results on DRD4 VNTR genotype effect. The present meta-analysis suggests DRD4 VNTR variation may be a risk factor for problematic alcohol use. Our findings are limited, however, by the absence of ancestry data from studies included in our analysis, precluding our ability to adjust for population stratification. Due to the likelihood of type I error in candidate gene approaches, our work highlights the critical need for studies with larger and more inclusive samples that account for sex and genetic ancestry to fully understand this relationship.
Topics: Alcohol Drinking; Alcoholism; Binge Drinking; Craving; Humans; Minisatellite Repeats; Receptors, Dopamine D4
PubMed: 31149768
DOI: 10.1111/adb.12770 -
Molecular Biology Reports Sep 2014An appropriate ratio of interleukin 1 beta to interleukin 1 receptor antagonist (IL1Ra) is required for successful pregnancy. Our objective was to study the genetic... (Meta-Analysis)
Meta-Analysis
An appropriate ratio of interleukin 1 beta to interleukin 1 receptor antagonist (IL1Ra) is required for successful pregnancy. Our objective was to study the genetic association between IL1RN variable numbers of tandem repeat (VNTR) polymorphism and recurrent pregnancy loss (RPL). To analyze the association between IL1RN VNTR allele and RPL, we investigated the IL1RN VNTR polymorphism in 136 RPL patients and in 200 healthy control women. Meta-analysis on this polymorphism was conducted to support our findings. PCR based approach was used to analyze IL1RN VNTR polymorphism and it was further confirmed by sequencing. Systematic review and meta-analysis was done using electronic database (Pub-Med, Google Scholar and Ovid) up to February 27, 2013. This meta-analysis was assessed by comprehensive meta-analysis software version 2. For meta-analysis 549 cases and 1,450 controls were included. The frequency of IL1RN genotype 2/2 was significantly higher in RPL compared to control group (AORs 3.10, 95 % CI 1.58-6.11, p = 0.001). The presence of rare allele also increased the risk of RPL significantly (ORs 1.63, 95 % CI 1.16-2.29, p = 0.004). The meta-analysis stratified by ethnicity showed that individuals with allele 2 had increased risk of RPL (OR 1.29, 95 % CI 1.04-1.61, p = 0.01), in Asians population by using fixed model. However the data of the present study clearly suggests that IL1RN VNTR polymorphism is a genetic risk factor for pregnancy loss in the study population.
Topics: Abortion, Spontaneous; Adult; Alleles; Case-Control Studies; Female; Genetic Predisposition to Disease; Genotype; Humans; India; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Minisatellite Repeats; Polymorphism, Genetic; Pregnancy; Risk Factors; White People; Young Adult
PubMed: 24952603
DOI: 10.1007/s11033-014-3443-8