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Acta Diabetologica Dec 2015A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes... (Meta-Analysis)
Meta-Analysis Review
AIMS
A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive.
METHODS
We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls.
RESULTS
For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of -23HphI on LADA.
CONCLUSIONS
Our results support the existence of associations of INS with T1D and LADA.
Topics: Adult; Autoimmune Diseases; Diabetes Mellitus, Type 1; Gene Frequency; Genetic Predisposition to Disease; Humans; Minisatellite Repeats; Polymorphism, Genetic
PubMed: 26362169
DOI: 10.1007/s00592-015-0805-1 -
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 -
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 -
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 -
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 -
Journal of the Neurological Sciences Jun 2011Serotonin is known to play an important role in the pathogenesis of migraine, but individual genetic association studies that examine the relationship between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Serotonin is known to play an important role in the pathogenesis of migraine, but individual genetic association studies that examine the relationship between polymorphisms of serotonin transporter (5-HTT) gene and migraine have yielded inconsistent results. This study aimed to evaluate the association between 5-HTT gene variants (including 5-HTTLPR, VNTR and SNP) and migraine using systematic review with meta-analysis.
METHODS
Relevant studies were identified by searching English and Chinese databases extensively. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and Egger's test and Funnel plot were used to assess publication bias. For family-based association studies, a descriptive analysis was carried out.
RESULTS
A total of 15 studies were identified for meta-analysis. It was found that the 5-HTT VNTR Stin2.12 allele or 12/12 genotype had an increased risk for migraine in the general population (Stin2.12 allele: OR, 95% CI: 1.34, 1.09-1.64, p=0.006; 12/12 genotype: OR, 95% CI: 1.55, 1.17-2.05, p=0.002), but there was no significant association between migraine and 5-HTTLPR or SNP rs2020942.
CONCLUSIONS
Existing evidence indicates that the 5-HTT VNTR polymorphism (mainly the STin2.12 genotype) is associated with an increased risk of migraine in the general population. Future studies with larger sample sizes will be necessary to confirm the present results.
Topics: Genetic Predisposition to Disease; Genotype; Humans; Migraine Disorders; Minisatellite Repeats; Polymorphism, Genetic; Risk Assessment; Serotonin; Serotonin Plasma Membrane Transport Proteins
PubMed: 21450309
DOI: 10.1016/j.jns.2011.03.016 -
Pharmacogenomics May 2009Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic... (Review)
Review
Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.
Topics: Alcohol Withdrawal Delirium; Alcoholism; Case-Control Studies; DNA, Complementary; Dopamine Plasma Membrane Transport Proteins; Environment; Family; Female; Genetic Variation; Humans; Male; Minisatellite Repeats; Racial Groups; Risk Factors; Sex Characteristics; Tandem Repeat Sequences
PubMed: 19450132
DOI: 10.2217/pgs.09.24 -
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