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BMC Psychiatry Jul 2014It is widely acknowledged that suicidal behavior (SB) has a genetic influence. As a consequence, molecular genetic studies have been mostly conducted on serotonergic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is widely acknowledged that suicidal behavior (SB) has a genetic influence. As a consequence, molecular genetic studies have been mostly conducted on serotonergic genes. One of the most promising candidate genes of this system is tryptophan hydroxylase (TPH). Although there have been several positive studies associating TPH genes and SB, the evidence is not entirely consistent. Therefore, we performed a meta-analysis to gain a better understanding into this issue.
METHODS
The meta-analysis was conducted with 37 articles of genetic association studies of TPH-1 (A218C and A779C) and TPH2 (G-703 T, A-473 T and G19918A) genes. To analyze the association of these variants with SB we used the following models: allelic, additive, dominant and recessive. In addition, we performed a sub-group analysis by Caucasian and Asian populations using the same four models.
RESULTS
TPH-1 gene variants showed a positive significant association with SB, but only in the fixed effects models. With regard to TPH-2 gene variants we could not find an association with SB.
CONCLUSIONS
The study provides evidence that A218C/A779C TPH-1 variants may be a risk factor to manifest SB at the clinical level, which is in agreement with previously reported meta-analyses. With regard to G-703 T/A-473 T/G19918A TPH-2 variants, our up-to-date meta-analysis could not detect any significant association between those genetic variants and SB. However, these results should be interpreted with caution since further studies need to be undertaken using larger sample sizes in different ethnic populations to confirm our findings.
Topics: Alleles; Humans; Polymorphism, Genetic; Risk Factors; Suicidal Ideation; Tryptophan Hydroxylase; White People
PubMed: 25005534
DOI: 10.1186/1471-244X-14-196 -
Human Reproduction Update 2013Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were... (Review)
Review
BACKGROUND
Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.
METHODS
Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.
RESULTS
Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P < 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P = 0.002) per T allele of rs12255372.
CONCLUSIONS
In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
Topics: Alleles; Cyclin-Dependent Kinase 5; Diabetes, Gestational; Female; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Secretion; Polymorphism, Single Nucleotide; Pregnancy; RNA-Binding Proteins; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Risk; Transcription Factor 7-Like 2 Protein; tRNA Methyltransferases
PubMed: 23690305
DOI: 10.1093/humupd/dmt013 -
Genes, Brain, and Behavior Oct 2011Autism and schizophrenia are highly heritable neurodevelopmental disorders, each mediated by a diverse suite of genetic and environmental risk factors. Comorbidity and... (Comparative Study)
Comparative Study Review
Autism and schizophrenia are highly heritable neurodevelopmental disorders, each mediated by a diverse suite of genetic and environmental risk factors. Comorbidity and familial aggregation of such neurodevelopmental disorders with other disease-related conditions can provide important insights into their etiology. Epidemiological studies have documented reduced rates of rheumatoid arthritis, a systemic autoimmune condition, in schizophrenia, and recent work has shown increased rates of rheumatoid arthritis in first-degree relatives of autistic individuals, especially mothers. Advances in understanding the genetic basis of rheumatoid arthritis have shown that much of the genetic liability to this condition is due to risk and protective alleles at the HLA DRB1 locus. These data allow robust testing of the hypotheses that allelic variation at DRB1 pleiotropically modulates risk of rheumatoid arthritis, autism and schizophrenia. Systematic review of the literature indicates that reported associations of DRB1 variants with these three conditions are congruent with a pleiotropic model: DRB1*04 alleles have been associated with increased risk of rheumatoid arthritis and autism but decreased risk of schizophrenia, and DRB1*13 alleles have been associated with protection from rheumatoid arthritis and autism but higher risk of schizophrenia. These convergent findings from genetics and epidemiology imply that a subset of autism and schizophrenia cases may be underlain by genetically based neuroimmune alterations, and that analyses of the causes of risk and protective effects from DRB1 variants may provide new approaches to therapy.
Topics: Arthritis, Rheumatoid; Autistic Disorder; Autoimmunity; Female; Genetic Variation; HLA-DRB1 Chains; Humans; Immunogenetic Phenomena; Male; Neuroimmunomodulation; Schizophrenia
PubMed: 21649858
DOI: 10.1111/j.1601-183X.2011.00710.x -
International Journal of Environmental... Nov 2022Risk and loss aversion are phenomena with an important influence on decision-making, especially in economic contexts. At present, it remains unclear whether both are... (Review)
Review
Risk and loss aversion are phenomena with an important influence on decision-making, especially in economic contexts. At present, it remains unclear whether both are related, as well as whether they could have an emotional origin. The objective of this review, following the PRISMA statements, is to find consistencies in the genetic bases of risk and loss aversion with the aim of understanding their nature and shedding light on the above issues. A total of 23 empirical research met the inclusion criteria and were included from PubMed and ScienceDirect. All of them reported genetic measures from human samples and studied risk and loss aversion within an economic framework. The results for risk aversion, although with many limitations, attributed mainly to their heterogeneity and the lack of control in the studies, point to the implication of multiple polymorphisms related to the regulation of the serotonergic and dopaminergic pathways. In general, studies found the highest levels of risk aversion were associated with alleles that are linked to lower (higher) sensitivity or levels of dopamine (serotonin). For loss aversion, the scarcity of results prevents us from drawing clear conclusions, although the limited evidence seems to point in the same direction as for risk aversion. Therefore, it seems that risk aversion could have a stable genetical base which, in turn, is closely linked to emotions, but more research is needed to answer whether this phenomenon is related to loss aversion, as well as if the latter could also have an emotional origin. We also provide recommendations for future studies on genetics and economic behavior.
Topics: Humans; Affect; Emotions; Polymorphism, Genetic; Dopamine; Alleles; Decision Making
PubMed: 36361187
DOI: 10.3390/ijerph192114307 -
PloS One 2013A large number of studies have investigated whether polymorphisms in the Toll-like receptor (TLR) genes are implicated in susceptibility to tuberculosis (TB) in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A large number of studies have investigated whether polymorphisms in the Toll-like receptor (TLR) genes are implicated in susceptibility to tuberculosis (TB) in different populations. However, the results are inconsistent and inconclusive.
METHODS
A literature search was conducted using the PubMed, EMBASE, Medline (Ovid), ISI Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI). A meta-analysis on the associations between the TLR1 G1805T, TLR2 T597C, T1350C, G2258A, and TLR6 C745T polymorphisms and TB risk was carried out by comparison using different genetic models.
RESULTS
In total, 16 studies from 14 articles were included in this review. In meta-analysis, significant associations were observed between the TLR2 2258AA (AA vs. AG+AG, OR 5.82, 95% CI 1.30-26.16, P = 0.02) and TLR6 745TT (TT vs. CT+CC, OR 0.61, 95% CI 0.39-0.97, P = 0.04) polymorphisms and TB risk. In the subgroup analysis by ethnicity, Africans and American Hispanic subjects with the TLR1 1805T allele had an increased susceptibility, whereas Asian and European subjects with the TLR2 2258A allele had an increased susceptibility to TB.
CONCLUSIONS
The meta-analysis indicated that TLR2 G2258A is associated with increased TB risk, especially in Asians and Europeans. TLR1 G1805T is associated with increased TB in Africans and American Hispanics. TLR6 C745T is associated with decreased TB risk. Our systematic review and meta-analysis reported an interesting preliminary conclusion, but this must be validated by future large-scale and functional studies in different populations.
Topics: Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 6; Toll-Like Receptors; Tuberculosis, Pulmonary
PubMed: 23691034
DOI: 10.1371/journal.pone.0063357 -
PloS One 2011Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition, we analysed 15 SNPs within the LEPR gene in the CoLaus study, assessing the interaction of the variants with sex.
METHODOLOGY/PRINCIPAL FINDINGS
We searched electronic databases, including population-based studies that investigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects. We furthermore performed meta-analyses of the genotype and allele frequencies in case-control studies. Results were stratified by SNP and by potential effect modifiers. CoLaus data were analysed by logistic and linear regressions and tested for interaction with sex. The meta-analysis of published data did not show an overall association between any of the tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R. Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians. In CoLaus, the rs10128072, rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight, waist circumference and fat mass in linear regressions.
CONCLUSIONS
Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight. Most studies were underpowered to detect small effect sizes. A potential effect modification by sex, population stratification, as well as the role of natural selection should be addressed in future genetic association studies.
Topics: Animals; Cohort Studies; Gene Frequency; Genotype; Humans; Overweight; Polymorphism, Single Nucleotide; Receptors, Leptin
PubMed: 22028824
DOI: 10.1371/journal.pone.0026157 -
Behavioral and Brain Functions : BBF Nov 2016The association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study was to perform a systematic review and meta-analysis to explore the relation between three polymorphisms of the DRD2 gene (C957T, TaqI and Ser311Cys) and schizophrenia.
METHODS
The search was made in PubMed and EBSCO databases (up to February 2016). The systematic review included 34 case-control association studies (34 for C957T, 16 for TaqI and 36 for Ser311Cys). The association analysis comprised the allelic, additive, dominant, and recessive genetic models. The meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.
RESULTS
The meta-analysis showed that TaqI (additive model: OR 0.57, 95% CI 0.30-1.14) and C957T (additive model: OR 0.75, 95% OR 0.58-0.97, recessive model: OR 0.79, 95% CI 0.64-0.98) exert a protective effect against developing schizophrenia. However, the sub-analysis for the C957T variant showed that this polymorphism exhibits a risk factor effect on Chinese individuals (allelic model: OR 1.33, 95% CI 1.04-1.70).
CONCLUSION
Our meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.
Topics: Alleles; Case-Control Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Receptors, Dopamine D2; Risk Factors; Schizophrenia
PubMed: 27829443
DOI: 10.1186/s12993-016-0114-z -
Asian Pacific Journal of Cancer... 2012Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations.
METHODS
Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated.
RESULTS
According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively).
CONCLUSION
This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.
Topics: Alleles; Case-Control Studies; Cytochrome P-450 CYP2D6; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Neoplasms; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 22994728
DOI: 10.7314/apjcp.2012.13.7.3165 -
International Journal of Environmental... Mar 2021Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin.... (Review)
Review
Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the gene, (GT) repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT) repeats based on transcriptional capacity should be further investigated.
Topics: Alleles; Genetic Predisposition to Disease; Heme Oxygenase-1; Humans; Infant, Newborn; Polymorphism, Single Nucleotide; Promoter Regions, Genetic
PubMed: 33805292
DOI: 10.3390/ijerph18073520 -
BMC Medical Genetics Jan 2014Nitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and physiologically critical steps of nephron function. Endothelial NOS (eNOS) gene has been considered a potential candidate gene to diabetic nephropathy (DN) susceptibility. Endothelial nitric oxide synthase gene (eNOS-3) polymorphisms have been associated with DN, however some studies do not confirm this association. The analyzed polymorphisms were 4b/4a, T-786C, and G986T.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used in this report. Case-control studies that had diabetic patients with DN as cases and diabetic patients without nephropathy as controls, as well as that evaluated at least one of the three polymorphisms of interest were considered eligible. All studies published up until December 31st, 2012 were identified by searching electronic databases. Hardy-Weinberg equilibrium assessment was performed. Gene-disease association was measured using odds ratio estimation based on the following genetic contrast/models: (1) allele contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co-dominant model.
RESULTS
Twenty-two studies were eligible for meta-analysis (4b/a: 15 studies, T-786C: 5 studies, and G984T: 12 studies). Considering 4b/a polymorphism, an association with DN was observed for all genetic models: allele contrast (OR = 1.14, CI: 1.04-1.25); additive (OR = 1.77, CI: 1.37-2.28); recessive (OR = 1.77, CI: 1.38-2,27); dominant (OR = 1.12, CI: 1.01-1.24), with the exception for co-dominance model. As well, T-786C polymorphism showed association with all models, with exception for co-dominance model: allele contrast (OR = 1.22, CI: 1.07-1.39), additive (OR = 1.52, CI: 1.18-1.97), recessive (OR = 1.50, CI: 1.16-1.93), and dominant (OR = 1.11, CI: 1.01-1.23). For the G894T polymorphism, an association with DN was observed in allelic contrast (OR = 1.12, CI: 1.03-1.25) and co-dominance models (OR = 1.13, CI: 1.04-1.37).
CONCLUSIONS
In the present study, there was association of DN with eNOS 4b/a and T-786C polymorphism, which held in all genetic models tested, except for co-dominance model. G894T polymorphism was associated with DN only in allele contrast and in co-dominance model. This data suggested that the eNOS gene could play a role in the development of DN.
Topics: Animals; Diabetic Nephropathies; Genetic Predisposition to Disease; Humans; Nitric Oxide Synthase Type III; Polymorphism, Genetic
PubMed: 24433471
DOI: 10.1186/1471-2350-15-9