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Frontiers in Endocrinology 2022The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity... (Meta-Analysis)
Meta-Analysis
G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis.
BACKGROUND
The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity indexes as well as serum lipid levels have been extensively investigated in various studies, but the results were inconsistent and even contradictory.
METHODS
PubMed, Google Scholar, Embase, Cochrane Library, Web of Science, Wanfang, CNKI and VIP databases were searched for eligible studies. The random-effTPDEects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in obesity indexes and serum lipid levels between the subjects with different genotypes in a dominant model. Heterogeneity among studies was assessed by Cochran's x-based Q-statistic test. Publication bias was identified by using Begg's test.
RESULTS
One hundred and twenty studies (70,317 subjects) and 33 studies (18,353 subjects) were identified in the analyses for the rs1801282 and rs3856806 polymorphisms, respectively. The G allele carriers of the rs1801282 polymorphism had higher levels of body mass index (SMD = 0.08 kg/m, 95% CI = 0.04 to 0.12 kg/m, < 0.001), waist circumference (SMD = 0.12 cm, 95% CI = 0.06 to 0.18 cm, < 0.001) and total cholesterol (SMD = 0.07 mmol/L, 95% CI = 0.02 to 0.11 mmol/L, < 0.01) than the CC homozygotes. The T allele carriers of the rs3856806 polymorphism had lower levels of low-density lipoprotein cholesterol (SMD = -0.09 mmol/L, 95% CI = -0.15 to -0.03 mmol/L, < 0.01) and higher levels of high-density lipoprotein cholesterol (SMD = 0.06 mmol/L, 95% CI = 0.02 to 0.10 mmol/L, < 0.01) than the CC homozygotes.
CONCLUSIONS
The meta-analysis suggests that the G allele of the rs1801282 polymorphism confers an increased risk of obesity and hypercholesterolemia, while the T allele of the rs3856806 polymorphism displays a protective role against dyslipidemia, which can partly explain the associations between these polymorphisms and cardiovascular disease.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier [CRD42022319347].
Topics: Alleles; Cholesterol, HDL; Dyslipidemias; Humans; Hypercholesterolemia; Obesity; PPAR gamma; Polymorphism, Single Nucleotide
PubMed: 35846293
DOI: 10.3389/fendo.2022.919087 -
Journal of Affective Disorders Jul 2022Exposure to traumatic experience represents one of the key environmental factors influencing the risk for several psychiatric disorders, in particular when suffered... (Review)
Review
Neurotrophic factors, childhood trauma and psychiatric disorders: A systematic review of genetic, biochemical, cognitive and imaging studies to identify potential biomarkers.
BACKGROUND
Exposure to traumatic experience represents one of the key environmental factors influencing the risk for several psychiatric disorders, in particular when suffered during childhood, a critical period for brain development, characterized by a high level of neuroplasticity. Abnormalities affecting neurotrophic factors might play a fundamental role in the link between childhood trauma (CT) and early life stress (ELS) and psychiatric disorders.
METHODS
A systematic review was conducted, considering genetic, biochemical and expression studies along with cognitive and brain structure imaging investigations, based on PubMed and Web of Science databases (available up until November 2021), to identify potential neuroplasticity related biomarkers associated both with CT/ELS and psychiatric disorders. The search was followed by data abstraction and study quality assessment (Newcastle-Ottawa Scale).
RESULTS
103 studies met our eligibility criteria. Among them, 65 were available for genetic, 30 for biochemical and 3 for mRNA data; 45 findings were linked to specific symptomatology/pathologies, 16 with various cognitive functions, 19 with different brain areas, 6 on methylation and 36 performed on control subjects for the Brain Derived Neurotrophic Factor (BDNF); whereas 4 expression/biochemical studies covered Neurotrophin 4 (NT-4), Vascular Endothelium Growth Factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), and Transforming Growth Factor β1 (TGF-β1).
LIMITATIONS
Heterogeneity of assessments (biological, psychological, of symptomatology, and CT/ELS), age range and ethnicity of samples for BDNF studies; limited studies for other neurotrophins.
CONCLUSIONS
Results support the key role of BDNF (in form of Met allele) as biomarker, both at genetic and biochemical level, in mediating the effect of CT/ELS in psychiatric disorders, passing through specific cognitive functions and specific brain region architecture.
Topics: Adverse Childhood Experiences; Biomarkers; Brain-Derived Neurotrophic Factor; Cognition; Humans; Mental Disorders; Molecular Biology
PubMed: 35378148
DOI: 10.1016/j.jad.2022.03.071 -
Molecular Genetics & Genomic Medicine Nov 2023Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with susceptibility to interstitial lung diseases (ILDs). In this study, we summarized relevant studies and applied a meta-analysis to explore whether the polymorphism of rs2609255 site of the FAM13A gene can be utilized to predict susceptibility to idiopathic pulmonary fibrosis (IPF) patients or rheumatoid arthritis-associated interstitial lung disease (RA-ILD) or silicosis patients in different populations for the first time.
METHODS
We compared the frequency of G allele on rs2609255 site of FAM13A between the control subjects and IPF or RA-ILD or silicosis patients from different races by using meta-analysis. Nine studies were involved in this meta-analysis, including five IPF studies, two RA-ILD studies, and two silicosis studies, and containing 14 subgroups. We conducted separate meta-analyses for different races.
RESULTS
In all individuals, a substantial link between the G allele of the FAM13A rs2609255 polymorphism and IPF (OR: 1.47, 95% CI: 1.33-1.63, p < 0.00001) was indicated. After dividing by ethnicity, the G allele was illustrated to be considerable correlation with IPF in Asian (OR: 2.63, 95% CI: 1.81-3.81, p < 0.00001) and with RA-ILD individuals (OR: 3.27, 95% CI: 1.26-8.49, p = 0.01). Conversely, there was no correlation with the G allele and IPF in European individuals (OR: 1.27, 95% CI: 0.89-1.83, p = 0.13) or silicosis in Chinese individuals (OR: 1.20, 95% CI: 0.99-1.46, p = 0.07).
CONCLUSION
This is the first meta-analysis that provides evidence that the rs2609255 of FAM13A might increase susceptibility to RA-ILD, and IPF especially in Asian but not in European individuals, and not be correlated with silicosis in Chinese individuals, which indicated the differences in susceptibility to disease by race were noteworthy.
Topics: Humans; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Polymorphism, Genetic; Arthritis, Rheumatoid; Silicosis; GTPase-Activating Proteins
PubMed: 37786320
DOI: 10.1002/mgg3.2279 -
Pharmaceutics Feb 2022Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted... (Review)
Review
Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted with small sample sizes, making it challenging to apply the findings clinically. Therefore, the purpose of this study is to perform a meta-analysis of the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. We searched three electronic databases, EMBASE, PubMed, and Web of Science, using search terms related to ABCG2 gene polymorphisms and rosuvastatin. In addition, we reviewed studies published before 12 August 2021, to examine the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. To examine the magnitude of the association, the log geometric mean difference (lnGM) and 95% confidence intervals (CIs) were calculated and interpreted as the antilogarithm of a natural logarithm (elnGM). The meta-analysis was performed using Review Manager (version 5.4) and R Studio (version 4.0.2). Subgroup analysis was performed according to race and the types of mean values. Among the 318 identified studies, a total of 8 studies involving 423 patients is included in this meta-analysis. The A allele carriers of ABCG2 421C>A showed 1.5 times higher in both AUC0-∞ (lnGM = 0.43; 95% CI = 0.35−0.50; p < 0.00001) and Cmax (lnGM = 0.42; 95% CI = 0.33−0.51; p < 0.00001) than non-carriers, while there was no significant difference in Tmax and half-life. There was no significance in the pharmacokinetic parameters of the subgroups using either ethnicity or mean values. This meta-analysis demonstrates that subjects carrying the A allele of ABCG2 421C>A show significantly increased AUC0-∞ and Cmax values compared to subjects with the CC genotype. Therefore, information about ABCG2 genotypes might be useful for individualized rosuvastatin therapy.
PubMed: 35335877
DOI: 10.3390/pharmaceutics14030501 -
The Journal of Gene Medicine Mar 2023In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic review and meta-analysis to reevaluate the evidence on this association.
METHODS
A comprehensive literature search was performed on PubMed, Web of Knowledge and the Cochrane library up to September 2022. Methodological study quality was assessed using the Newcastle-Ottawa Scale and the credibility of significant pooled odds ratios (ORs) was estimated by the false positive report probability and the Bayesian false discovery probability.
RESULTS
Twelve studies published from 2009 to 2022 fulfilled the inclusion criteria. In the overall analysis, the ε4 allele was found to confer an increased risk of RPL compared to the ε3 allele (OR 1.60, 95% CI 1.00-2.55, p = 0.049) and women carrying the ApoE ε4 allele displayed a higher risk of RPL compared with those carrying the ε2 and ε3 alleles (OR 1.75, 95% CI 1.06-2.87, p = 0.028). Subgroup analysis based on subjects' ethnicity revealed that these associations were restricted to the Asian population (ε4 allele vs. ε3 allele, OR 5.93, 95% CI 1.79-19.61, p = 0.004; ε4 allele carriers vs. carriers of ε2 and ε3 alleles, OR 8.42, 95% CI 1.47-48.12, p = 0.017). None of the associations detected were found to be noteworthy under false positive report probability or Bayesian false discovery probability at a prior probability of 0.001.
CONCLUSIONS
This updated meta-analysis highlights an association between maternal ApoE genotype and RPL risk in Asians, but not in Caucasians. Further case-control studies are warranted in women of Asian ancestry to exclude the possibility of false-positive findings.
Topics: Female; Humans; Abortion, Habitual; Apolipoproteins E; Bayes Theorem; Genotype; Heterozygote
PubMed: 36479790
DOI: 10.1002/jgm.3467 -
Biological Trace Element Research Feb 2022To evaluate the association between selenoprotein gene polymorphisms and Kashin-Beck disease (KBD) susceptibility through a systematic review and updated meta-analysis.... (Meta-Analysis)
Meta-Analysis Review
To evaluate the association between selenoprotein gene polymorphisms and Kashin-Beck disease (KBD) susceptibility through a systematic review and updated meta-analysis. PubMed, Google Scholar, Cochrane library, and Chinese National Knowledge Infrastructure (CNKI) were electronically searched using the terms "selenoprotein" and "Kashin-Beck disease" or "KBD" with a search time from the establishment of the database to January 2021. The Newcastle-Ottawa Scale (NOS) was used for methodological quality evaluation of the included studies. Stata 14.0 software was used to pooled odds ratio (OR) and 95% confidence interval. There were a total of eight included case-control studies covering 2025 KBD patients and 1962 controls. Meta-analysis results show that the pooled odds ratios (OR) and 95% confidence intervals (CI) for DIO2 (rs225014) were 0.69 (0.52, 0.91), 0.69 (0.50, 0.96), and 0.72 (0.52, 0.99) in the allele, heterozygote, and dominant models, respectively. The OR and 95%CI for SEPS1 (-105G>A) were 2.47 (1.85, 3.29), 9.36 (4.58, 19.12), 2.17 (1.53, 3.08), and 8.60 (4.25, 17.38) in the allele, homozygote, dominant, and recessive models, respectively. In addition, the OR and 95%CI for Sep15 (rs5859) were 2.05 (1.06, 3.96) in the allele model. These results illustrate that there was a significant association between DIO2 (rs225014), SEPS1 (-105G>A), Sep15 (rs5859), and KBD. For GPX1 (rs1050450, rs1800668, rs3811699), DIO2 (rs225014, rs1352815, rs1388382), TrxR2 (rs1139793, rs5746841), GPX4 (rs713041, rs4807542), and SEPP1 (rs7579, 25191g/a), there was no significant statistical difference between the KBD and control groups (P>0.05). We conclude that the DIO2 (rs225014), SEPS1 (-105G>A), and Sep15 (rs5859) gene polymorphism are associated with susceptibility to KBD.
Topics: Asian People; Case-Control Studies; Genetic Predisposition to Disease; Humans; Kashin-Beck Disease; Polymorphism, Single Nucleotide; Selenoprotein P; Selenoproteins
PubMed: 33844169
DOI: 10.1007/s12011-021-02705-2 -
Nutrition Journal Sep 2022Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association... (Review)
Review
BACKGROUND
Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors.
METHODS
A systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021.
RESULTS
Thirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status.
CONCLUSION
The modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory.
PROSPERO REGISTRATION NUMBER
CRD42020196327.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Fats; Fatty Acids; Humans; Insulin; Insulin Resistance; Life Style; Polymorphism, Single Nucleotide; T Cell Transcription Factor 1; Transcription Factor 7-Like 2 Protein
PubMed: 36155628
DOI: 10.1186/s12937-022-00813-w -
Life (Basel, Switzerland) Aug 2023Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total...
Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor ( < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.
PubMed: 37629534
DOI: 10.3390/life13081677 -
Scientific Reports Jun 2022Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic... (Meta-Analysis)
Meta-Analysis
Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.
Topics: Autoantibodies; Autoimmunity; Gene Frequency; HLA-DRB1 Chains; Humans; Immunoglobulin G; Pemphigus
PubMed: 35654912
DOI: 10.1038/s41598-022-13042-2 -
Frontiers in Psychiatry 2022We aimed to examine the association of polymorphisms with the risk of suicide behavior (SB).
OBJECTIVES
We aimed to examine the association of polymorphisms with the risk of suicide behavior (SB).
DESIGN
Systematic review and meta-analysis.
METHOD
All relevant studies that evaluated the association between the A218C (rs1800532), A779C (rs1799913) and A6526G (rs4537731) polymorphisms and the susceptibility to SB published up to September 2021 were identified through a comprehensive systematic search in PubMed, Scopus, EBSCO and Science Direct electronic databases. The association between gene polymorphisms and SB was evaluated using inherence models by odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses, heterogeneity analyses, and publication bias were also tested in this meta-analysis.
RESULTS
The meta-analysis for A218C revealed an increased risk of SB in the dominant model (OR = 1.11, 95%CI 1.01-1.22). We also observed a positive association in the allelic (OR = 1.13, 95%CI 1.05-1.21), homozygous (OR = 1.22, 95%CI 1.06-1.40), heterozygous (OR = 1.21, 95%CI 1.08-1.37) and dominant (OR = 1.21, 95%CI 1.09-1.34) inherence models with the suicide attempt. Additionally, in the heterozygous (OR = 0.84, 95%CI 0.73-0.97) and dominant (OR = 0.79, 95%CI 0.68-0.91) inherence models we detected an association with completed suicide. Based on ethnicity, an association of SB in the European population also was observed (OR = 1.29, 95%CI 1.12-1.51). However, for both A779C and A6526G polymorphisms we did not find evidence of an association with SB.
CONCLUSION
This meta-analysis suggests that the A218C polymorphism of gene could be a possible risk factor of SB. Future large-scale studies are required to analyze the molecular mechanisms by which affect the susceptibility of developing suicide behavior.
PubMed: 35928776
DOI: 10.3389/fpsyt.2022.932135