-
Irish Journal of Medical Science Feb 2018Thiopurines, commonly used to treat autoimmune conditions and cancer, can be limited by life-threatening leucopenia. However, whether NUDT15 (nucleoside... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thiopurines, commonly used to treat autoimmune conditions and cancer, can be limited by life-threatening leucopenia. However, whether NUDT15 (nucleoside diphosphate-linked moiety X-type motif 15) is associated with thiopurine-induced leucopenia in Asians is controversial.
METHODS
Relevant studies in English that were published until July 10, 2016 were identified through PubMed, EMbase, and other web knowledge databases. Study quality was assessed according to the Newcastle-Ottawa Scale (NOS) criteria. Summary risk ratio (RR) and 95% confidence intervals (CI) were estimated based on a fixed-effects model or a random-effects model, depending on the absence or presence of significant heterogeneity.
RESULTS
Seven studies of 1138 patients met our inclusion criteria. Random-effects model meta-analysis provided evidence that T carriers of NUDT15 c.415C>T were significantly correlated with high incidences of thiopurine-induced leukocytopenia [CT + TT vs. CC: RR = 3.79, 95%CI (2.64 ~ 5.44), P < 0.00001]. This correlation was especially strong in TT patients, where it was found to be significantly increased by 6.54-fold compared with CC patients [TT vs. CC: RR = 6.54, 95%CI (3.34 ~ 12.82), P < 0.00001]. We also found that the NUDT15 c.415C>T variant was common in Asians and Hispanics, but rare in Europeans and Africans; the frequency of the NUDT15 c.415C>T distribution varied substantially by race/ethnicity.
CONCLUSION
The results of this meta-analysis confirm that NUDT15 c.415C>T may be an important predictor of thiopurine-induced leukocytopenia in Asians. Genotype targeting of NUDT15 c.415C>T before initiating thiopurine treatment may be useful to limit leukocytopenia.
Topics: Alleles; Asian People; Genetic Predisposition to Disease; Genotype; Humans; Leukopenia; Pyrophosphatases; Risk Factors
PubMed: 28470355
DOI: 10.1007/s11845-017-1608-x -
Pediatric Pulmonology Aug 2014A number of small studies have suggested a relationship between vitamin D status and severe acute lower respiratory tract infection (ALRI), including RSV-bronchiolitis.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A number of small studies have suggested a relationship between vitamin D status and severe acute lower respiratory tract infection (ALRI), including RSV-bronchiolitis. The objective of this study was to evaluate the relationship between vitamin D receptor (VDR) polymorphism and severe RSV-bronchiolitis through a systemic literature review and meta-analysis.
METHODS
A comprehensive electronic literature search was conducted to identify all studies published before January 2013. Two reviewers independently screened all abstracts, followed by the full text of potential articles to evaluate eligibility. Study methodological quality was evaluated using the Newcastle Ottawa scale and individual component analysis. Meta-analysis evaluated associations at the allele and genotype levels.
RESULTS
Of 803 studies identified from our literature search, three met eligibility criteria. Two VDR polymorphisms were included in more than one study: TaqI (rs731236) and FokI (rs2228570). All three reported a positive relationship between the FokI minor allele and disease with random effects meta-analyses demonstrating a statistically significant relationship (OR 1.52, CI: 1.12, 2.05). Genotype analysis was highly suggestive of a dominant or incomplete dominance model with combined odds ratios for fF (OR 1.73, CI: 0.92-3.36) and ff (OR 2.24, CI: 0.98-5.14) compared to the FF genotype. No association between TaqI and severe RSV-bronchiolitis was evident at the allele or genotype level.
CONCLUSIONS
Available literature supports an association between the FokI polymorphism and severe RSV disease. Determination of VDR receptor polymorphism status could help predict high-risk infants who might benefit from preventive measures.
Topics: Alleles; Bronchiolitis, Viral; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Respiratory Syncytial Virus Infections; Severity of Illness Index
PubMed: 24019226
DOI: 10.1002/ppul.22877 -
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 -
European Neuropsychopharmacology : the... Oct 2013Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly... (Review)
Review
Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly heritable. Neurobiological evidence implicates serotonergic dysfunction in suicidality, stimulating genetic research to focus on genes related to the serotonergic system. In this paper, we review evidence from studies examining the association between various serotonergic genes (Tryptophan Hydroxylase genes: TPH1; TPH2, Serotonin Transporter gene: 5-HTTLPR in SLC6A4, Serotonin Receptor genes: HTR1A, HTR2A, HTR1B, HTR2C and Monoamine Oxidase A gene: MAOA) and suicidal behavior. The data show associations between variation on the TPH1 gene and 5-HTTLPR gene and violent suicidal behavior in Caucasian populations, with the least inconsistencies. Results are mixed for the TPH2 gene and serotonin receptor genes, but for some genes, studies that include haplotypic analyses or that examine a larger coding region of the genes tend to provide more reliable results. Findings on endophenotypes of suicidality, such as aggression and impulsivity traits, show positive associations for the TPH1, HTR2A, and MAOA genes, but need further replication, since negative associations are also occasionally reported. Since genes can only partially explain suicidal risk, several studies during the past decade have tried to incorporate environmental factors in the susceptibility model. Studies to date show that variation on the 5-HTTLPR, MAOA and HTR2A gene can interact with stressful life events to increase risk for suicidal behavior. Limitations of case-control studies are discussed and future considerations are put forward with regard to endophenotypic measurements and gene-environment interactions.
Topics: Alleles; Animals; Brain; Case-Control Studies; Endophenotypes; Evidence-Based Medicine; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Monoamine Oxidase; Nerve Tissue Proteins; Neurons; Protein Isoforms; Receptors, Serotonin; Self-Injurious Behavior; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase; Suicide Prevention
PubMed: 23742855
DOI: 10.1016/j.euroneuro.2013.03.013 -
Parasitology International Dec 2011Several human genetic variants, HLA antigens and alleles are reportedly linked to post-schistosomal hepatic disorder (PSHD), but the results from these reports are... (Meta-Analysis)
Meta-Analysis Review
Several human genetic variants, HLA antigens and alleles are reportedly linked to post-schistosomal hepatic disorder (PSHD), but the results from these reports are highly inconclusive. In order to estimate overall associations between human genetic variants, HLA antigens, HLA alleles and PSHD, we systematically reviewed and performed a meta-analysis of relevant studies in both post-schistosomal hepatic disorder and post-schistosomal non-hepatic disorder patients. PubMed, Scopus, Google Scholar, The HuGE Published Literature database, Cochrane Library, and manual search of reference lists of articles published before July 2009 were used to retrieve relevant studies. Two reviewers independently selected articles and extracted data on study characteristics and data regarding the association between genetic variants, HLA antigens, HLA alleles and PSHD in the form of 2×2 tables. A meta-analysis using fixed-effects or random-effects models to pooled odds ratios (OR) with corresponding 95% confidence intervals were calculated only if more than one study had investigated particular variation. We found 17 articles that met our eligibility criteria. Schistosoma mansoni and Schistosoma japonicum were reported as the species causing PSHD. Since human genetic variants were only investigated in one study, these markers were not assessed by meta-analysis. Thus, only HLA-genes (a total of 66 HLA markers) were conducted in the meta-analysis. Our meta-analysis showed that human leucocyte antigens HLA-DQB1*0201 (OR=2.64, P=0.018), DQB1*0303 (OR=1.93, P=0.008), and DRB1*0901 (OR=2.14, P=0.002) alleles and HLA-A1 (OR=5.10, P=0.001), A2 (OR=2.17, P=0.005), B5 (OR=4.63, P=0.001), B8 (OR=2.99, P=0.02), and B12 (OR=5.49, P=0.005) serotypes enhanced susceptibility to PSHD, whereas HLA-DQA1*0501 (OR=0.29, P≤0.001) and DQB1*0301 (OR=0.58, P=0.007) were protective factors against the disease. We further suggested that the DRB1*0901-DQB1*0201, DRB1*0901-DQB1*0303 and A1-B8 haplotypes enhanced susceptibility to PSHD, whereas DQA1*0501-DQB1*0301 linkage decreased the risk of PSHD. The result improved our understanding of the association between the HLA loci and PSHD with regard to pathogenic or protective T-cells and provided novel evidence that HLA alleles may influence disease severity.
Topics: Africa; Alleles; Animals; Asia; Databases, Bibliographic; Genetic Linkage; Genetic Predisposition to Disease; Genotype; Haplotypes; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Liver Diseases; Odds Ratio; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Severity of Illness Index; South America
PubMed: 21664486
DOI: 10.1016/j.parint.2011.05.008 -
Public Health Genomics Sep 2022The tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene produces ubiquitin-editing protein A20, which inhibits nuclear factor-κB (NF-κB) activation in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene produces ubiquitin-editing protein A20, which inhibits nuclear factor-κB (NF-κB) activation in a variety of signaling pathways. We examined the association between TNFAIP3 polymorphisms and rheumatoid arthritis (RA) susceptibility.
METHODS
MEDLINE, Embase, Scopus, and Web of Science were searched for available articles on TNFAIP3 polymorphisms in RA patients from inception until July 11, 2022. We included case-control studies on the association between rs2230926 and rs5029937 polymorphisms of TNFAIP3 and RA, and we excluded studies that contained overlapping data. We scored the quality of each study included based on the Newcastle-Ottawa Scale. Meta-analyses evaluated the association between TNFAIP3 polymorphisms and RA susceptibility in diverse ethnic populations and was verified through trial sequential analysis (TSA). This meta-analysis was registered in the PROSPERO register (number: CRD42022345160). There was no funding source.
RESULTS
Seventeen studies were chosen for meta-analysis. Ten studies for rs2230926, and seven for rs5029937. An association was noted between TNFAIP3 rs2230926 G allele and RA in all subjects (odds ratio [OR] = 1.389; 95% confidence interval [CI] = 1.161-1.662; p < 0.001). Ethnicity-specific analysis showed significant association of rs2230926 G allele with RA in Europeans and Asians (OR = 1.642; 95% CI = 1.099-2.452; p = 0.015; OR = 1.404; 95% CI = 1.262-1.562; p < 0.001). An association was also noted between TNFAIP3 rs5029937 T allele and RA in all subjects (OR = 1.389; 95% CI = 1.207-1.785; p < 0.001). An ethnicity-specific meta-analysis revealed a significant association of the rs5029937 T allele with RA in Europeans and Asians. Dominant model analysis showed the same pattern for TNFAIP3 rs2230926 G and rs5029937 T alleles in Europeans and Asians, suggesting an association between rs2230926 G and rs5029937. TSA indicated a robust association between the TNFAIP3 polymorphisms and the risk of RA.
CONCLUSION
TNFAIP3 rs2230926 and rs5029937 polymorphisms are associated with RA susceptibility in European and Asian populations. However, the data were not stratified by parameters such as rheumatoid factor status, disease activity, or environmental variables.
PubMed: 36096098
DOI: 10.1159/000526212 -
BMC Medical Genomics Apr 2021Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors.
METHODS
We performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese.
RESULTS
Systematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found that TNF rs1800629 A allele carriers and CYP17A1 rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33-0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40-0.79), respectively, across populations. Overall, FST (follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neither TIMP2 (TIMP metallopeptidase inhibitor 2) rs8179090 nor CYP1A1 rs4646903 (pOR: 0.96, 95% CI: 0.80-1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3' UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation.
CONCLUSIONS
This systematic review and meta-analysis suggest that genes influencing inflammatory responses, specifically TNF, and genes influencing the function and activity of sebaceous glands, specifically CYP17A1 and FST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments.
Topics: Acne Vulgaris; Alleles; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide
PubMed: 33849530
DOI: 10.1186/s12920-021-00953-8 -
Oncotarget Aug 2016mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to... (Meta-Analysis)
Meta-Analysis Review
mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed a systematic review and updated meta-analysis of the available evidence regarding the relationship between mTOR single nucleotide polymorphisms (SNPs) and cancer risk. Up to November 2015, 23 original publications were identified covering 20 mTOR SNPs, of which seven SNPs (rs2536, rs2295080, rs1883965, rs1034528, rs17036508, rs3806317 and rs1064261) were included in the final meta-analysis. We estimated the summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for mTOR polymorphisms and cancer risk, and used the model-free approach to investigate the biological effect of each polymorphism. Our meta-analysis found that rs1883965, rs1034528, and rs17036508 were correlated with increased cancer risk in the complete over-dominant model (rs1883965 GA versus GG/AA: fixed-effects OR=1.15, 95% CI 1.02-1.29; rs1034528 GC versus GG/CC: fixed-effects OR=1.30, 95% CI 1.13-1.48; rs17036508 TC versus CC/TT: fixed-effects OR=1.23, 95% CI 1.06-1.43). Stratifying analyses by cancer type, we found that the rs2295080 G allele was associated with a significantly higher risk of acute leukemia in the recessive model (GG versus GT/TT: fixed-effects OR=2.08, 95% CI 1.34-3.22) and a lower risk of genitourinary cancers in the dominant model (TG/GG versus TT: fixed-effects OR=0.77, 95% CI 0.68-0.86). Interestingly, further expression analysis showed that homozygous variant genotype carriers of rs1883965, rs1034528 and rs17036508 had lower mTOR transcript levels, based on HapMap data.
Topics: Alleles; Computational Biology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genotype; Humans; Neoplasms; Odds Ratio; Polymorphism, Single Nucleotide; TOR Serine-Threonine Kinases
PubMed: 27462867
DOI: 10.18632/oncotarget.10805 -
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 -
Cytokine Jan 2022Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the small intestine, colon, and rectum. We evaluated associations between the interleukin... (Meta-Analysis)
Meta-Analysis
Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the small intestine, colon, and rectum. We evaluated associations between the interleukin 10 (IL-10) rs3024505 polymorphism and IBD, ulcerative colitis (UC), and Crohn's disease (CD) by meta-analysis. All peer-reviewed manuscripts concerning the relationship between IL-10_rs3024505 and IBD identified by searing the PubMed, Cochrane Library, EMBASE, and Chinese Medical Database were examined. The association between IL-10_rs3024505 and IBD was evaluated in allele (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Associations were also conducted on IBD subtypes, CD and UC, and ethnicity (Non-Europeans and Europeans) subgroups. The meta-analysis included 13 studies, 8552 cases (IBD patients), and 12,830 healthy controls. Subgroup analysis of IBD (UC and CD) revealed heterogeneity in AG, DG, and HTG but no heterogeneity in RG or HMG. Moreover, AG, DG, and HTG did not show publication bias in IBD, CD, or UC, but RG and HMG exhibited publication bias. No heterogeneity and no publication bias were found among the five genetic models by a subgroup analysis of Non-Europeans and European ethnicities. The minor allele(T) of rs3024505 was significantly related to IBD: 1.37 (1.30-1.45) for AG, 2.06 (1.74-2.45) for RG, 1.39 (1.27-1.52) for DG, 2.25 (1.89-2.67) for HMG, and 1.32 (1.23-1.40) for HTG (all P < 0.00001). In the subgroup analysis of ethnicity, there was a significant effect of rs3024505 on IBD in Europeans but not non-Europeans: 1.38 (1.31-1.46) for AG, 2.07 (1.73-2.48) for RG, 1.39 (1.31-1.49) for DG, 2.26 (1.89-2.71) for HMG, and 1.33 (1.24-1.42) for HTG in Europeans (all P < 0.00001). Sensitivity analysis showed no dominant study in Europeans, but one study had a dominant impact in Non-Europeans. In conclusion, IL-10_rs3024505 polymorphism confers susceptibility to CD and UC in Europeans, but its impact should have conducted more studies in Non-Europeans.
Topics: Alleles; Animals; Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases; Interleukin-10; Polymorphism, Single Nucleotide
PubMed: 34628128
DOI: 10.1016/j.cyto.2021.155721