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Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
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 -
Anesthesiology Dec 2023Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants of interest will help investigators understand the potential effects of genetic variation.
METHODS
This article is a systematic review of genetic variants associated with postsurgical pain in humans, assessing association with postsurgical pain scores and opioid use in both acute (0 to 48 h postoperatively) and chronic (at least 3 months postoperatively) settings. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from 2000 to 2022 for studies using search terms related to genetic variants and postsurgical pain in humans. English-language studies in adult patients examining associations of one or more genetic variants with postsurgical pain were included. The primary outcome was association of genetic variants with either acute or chronic postsurgical pain. Pain was measured by patient-reported pain score or analgesic or opioid consumption.
RESULTS
A total of 163 studies were included, evaluating 129 unique genes and 594 unique genetic variants. Many of the reported significant associations fail to be replicated in other studies. Meta-analyses were performed for seven variants for which there was sufficient data (OPRM1 rs1799971; COMT rs4680, rs4818, rs4633, and rs6269; and ABCB1 rs1045642 and rs2032582). Only two variants were associated with small differences in postsurgical pain: OPRM1 rs1799971 (for acute postsurgical opioid use standard mean difference = 0.25; 95% CI, 0.16 to 0.35; cohort size, 8,227; acute postsurgical pain score standard mean difference = 0.20; 95% CI, 0.09 to 0.31; cohort size, 4,619) and COMT rs4680 (chronic postsurgical pain score standard mean difference = 0.26; 95% CI, 0.08 to 0.44; cohort size, 1,726).
CONCLUSIONS
Despite much published data, only two alleles have a small association with postsurgical pain. Small sample sizes, potential confounding variables, and inconsistent findings underscore the need to examine larger cohorts with consistent outcome measures.
Topics: Adult; Humans; Analgesics, Opioid; Polymorphism, Single Nucleotide; Pain, Postoperative; Analgesics
PubMed: 37774411
DOI: 10.1097/ALN.0000000000004677 -
Pain Physician Sep 2023Responsiveness to opioid analgesics differs among patients with acute postoperative pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Responsiveness to opioid analgesics differs among patients with acute postoperative pain.
OBJECTIVE
Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids.
STUDY DESIGN
An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain.
METHODS
PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021.
RESULTS
Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human μ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms.
LIMITATIONS
Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis.
CONCLUSIONS
In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia.
KEY WORDS
Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
Topics: Humans; Analgesics, Opioid; Catechol O-Methyltransferase; Cytochrome P-450 CYP3A; Pain, Postoperative; Polymorphism, Single Nucleotide
PubMed: 37774182
DOI: No ID Found -
Medicine Sep 2023This systemic review and meta-analysis seeks to systematically analyze and summarize the association between non-coding RNA polymorphisms and ovarian cancer risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systemic review and meta-analysis seeks to systematically analyze and summarize the association between non-coding RNA polymorphisms and ovarian cancer risk.
METHODS
We searched PubMed, Web of Science and CNKI for available articles on non-coding RNA polymorphisms in patients with ovarian cancer from inception to March 1, 2023. The quality of each study included in the meta-analysis was rated according to the Newcastle-Ottawa Scale.Odds ratios (ORs) with their 95% confidence intervals (95% CI) were used to assess associations. Chi-square Q-test combined with inconsistency index (I2) was used to test for heterogeneity among studies. Lastly, trial sequential analysis (TSA) software was used to verify the reliability of meta-analysis results, and in-silico miRNA expression were also performed. The meta-analysis was registered with PROSPERO (No. CRD42023422091).
RESULTS
A total of 17 case-control studies with 18 SNPs were selected, including 2 studies with H19 rs2107425 and HOTAIR rs4759314, and 5 studies with miR-146a rs2910164 and miR-196a rs11614913. Significant associations were found between H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 and ovarian cancer risk. Three genetic models of H19 rs2107425 (CT vs TT (heterozygote model): OR = 1.36, 95% CI = 1.22-1.52, P < .00001; CC + CT vs TT (dominant model): OR = 1.12, 95% CI = 1.02-1.24, P = .02; and CC vs CT + TT (recessive model): OR = 1.23, 95% CI = 1.16-1.31, P < .00001), 2 genetic models of miR-146a rs2910164 (allele model: OR = 1.75, 95% CI = 1.05-2.91, P = .03; and heterozygote model: OR = 0.33, 95% CI = 0.11-0.98, P = .05), 3 genetic models of miR-196a rs11614913 (allele model: OR = 0.70, 95% CI = 0.59-0.82, P < .0001; dominant model: OR = 1.62, 95% CI = 1.18-2.24, P = .0001; and recessive model: OR = 0.70, 95% CI = 0.57-0.87, P = .03) were statistically linked to ovarian cancer risk. Subgroup analysis for miR-146a rs2910164 was performed according to ethnicity. No association was found in any genetic model. The outcomes of TSA also validated the findings of this meta-analysis.
CONCLUSION
This study summarizes that H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 polymorphisms are significantly linked with the risk of ovarian cancer, and moreover, large-scale and well-designed studies are needed to validate our result.
Topics: Female; Humans; Reproducibility of Results; Genetic Predisposition to Disease; MicroRNAs; Polymorphism, Single Nucleotide; Ovarian Neoplasms; Case-Control Studies
PubMed: 37773807
DOI: 10.1097/MD.0000000000035257 -
Nutrients Sep 2023The genetic risk score (GRS) is an important tool for estimating the total genetic contribution or susceptibility to a certain outcome of interest in an individual,... (Review)
Review
The genetic risk score (GRS) is an important tool for estimating the total genetic contribution or susceptibility to a certain outcome of interest in an individual, taking into account their genetic risk alleles. This study aims to systematically review the association between the GRS of low vitamin D with different noncommunicable diseases/markers. The article was first registered in PROSPERO CRD42023406929. PubMed and Embase were searched from the time of inception until March 2023 to capture all the literature related to the vitamin D genetic risk score (vD-GRS) in association with noncommunicable diseases. This was performed using comprehensive search terms including "Genetic Risk Score" OR "Genetics risk assessment" OR "Genome-wide risk score" AND "Vitamin D" OR 25(HO)D OR "25-hydroxyvitamin D". Eleven eligible studies were included in this study. Three studies reported a significant association between vD-GRS and metabolic parameters, including body fat percentage, body mass index, glycated hemoglobin, and fasting blood glucose. Moreover, colorectal cancer overall mortality and the risk of developing arterial fibrillation were also found to be associated with genetically deprived vitamin D levels. This systematic review highlights the genetic contribution of low-vitamin-D-risk single nucleotides polymorphisms (SNPs) as an accumulative factor associated with different non-communicable diseases/markers, including cancer mortality and the risk of developing obesity, type 2 diabetes, and cardiovascular diseases such as arterial fibrillation.
Topics: Humans; Noncommunicable Diseases; Diabetes Mellitus, Type 2; Vitamin D; Vitamins; Risk Factors
PubMed: 37764823
DOI: 10.3390/nu15184040 -
Medicine Sep 2023To investigate the association between sepsis and the vitamin D receptor (VDR) gene polymorphisms. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To investigate the association between sepsis and the vitamin D receptor (VDR) gene polymorphisms.
METHODS
Databases including PubMed, Cochrane Library, EMbase, CNKI, Wanfang Data, and VIP Data were systematically searched. The association was assessed using odds ratios (ORs), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.4.
RESULTS
We identified a total of 5 studies. The relationship between VDR gene polymorphisms (Apa I, Bsm I, Taq I, and Fok I), and incidence of sepsis was investigated. The results of this meta-analysis showed that the allelic contrast model (F vs f, P = .03, OR = 0.65, 95% CI = 0.44-0.95), dominant genetic model (FF vs Ff + ff, P = .02, OR = 0.53, 95% CI = 0.30-0.91), and codominance genetic model (FF vs ff, P = .03, OR = 0.39, 95% CI = 0.16-0.91) of VDR Fok I locus increased the risk of sepsis, and the lack of association between the VDR Fok I gene polymorphism and the risk assessment of sepsis, based on the ethnic subgroup analysis, might be attributable to the small sample size. The risk of sepsis with Apa I, Bsm I, and Taq I did not appear to be correlated.
CONCLUSION SUBSECTIONS
This meta-analysis revealed that the VDR Fok I polymorphism is closely associated with the susceptibility to sepsis, and patients with sepsis have lower 25-hydroxyvitamin D levels. VDR Fok I gene mutations may change the risk of sepsis.
Topics: Humans; Alleles; Calcifediol; Polymorphism, Genetic; Receptors, Calcitriol; Sepsis
PubMed: 37746941
DOI: 10.1097/MD.0000000000035130 -
Frontiers in Oncology 2023Previous genetic-epidemiological studies considered (rs2736100), (rs4295627), (rs4977756) and (rs6010620) gene polymorphisms as the risk factors specific to glioma....
BACKGROUND
Previous genetic-epidemiological studies considered (rs2736100), (rs4295627), (rs4977756) and (rs6010620) gene polymorphisms as the risk factors specific to glioma. However, the data samples of previous genetic-epidemiological studies are modest to determine whether they have definite association with glioma.
METHOD
The study paid attention to systematically searching databases of PubMed, Embase, Web of Science (WoS), Scopus, Cochrane Library and Google Scholars. Meta-analysis under 5 genetic models, namely recessive model (RM), over-dominant model (O-DM), allele model (AM), co-dominant model (C-DM) and dominant model (DM) was conducted for generating odds ratios (ORs) and 95% confidence intervals (CIs). That was accompanied by subgroup analyses according to various racial groups. The software STATA 17.0 MP was implemented in the study.
RESULT
21 articles were collected. According to data analysis results, in four genetic models (AM, RM, DM and C-DM) gene rs2736100 polymorphism, gene rs4295627 polymorphism, gene rs4977756 polymorphism and gene rs6010620 polymorphisms increased the risk of glioma in Caucasians to different degrees. In Asian populations, the gene rs4295627 polymorphism and gene rs4977756 polymorphism did not exhibit a relevance to the risk of glioma. It is suggested to cautiously explain these results as the sample size is small.
CONCLUSION
The current meta-analysis suggested that the SNP of (rs2736100), (rs4295627), (rs4977756) and (rs6010620) genes in glioma might increase risk of glioma, but there are ethnic differences. Further studies evaluating these polymorphisms and glioma risk are warranted.
PubMed: 37746290
DOI: 10.3389/fonc.2023.1180099 -
Lipids in Health and Disease Sep 2023Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C.
METHODS
The database "Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM" were retrieved to identify the literature. The quality of the selected literature was evaluated using the "the Newcastle-Ottawa Scale" (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by "Cochran's Q and I", with I ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used "Funnel plots", "Egger's tests" and "Begg's tests" to evaluate biases in the literature.
RESULTS
The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467-29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger's and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable.
CONCLUSIONS
Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.
Topics: Humans; Carrier Proteins; Fatty Liver; Genotype; Hepacivirus; Hepatitis C
PubMed: 37726765
DOI: 10.1186/s12944-023-01916-x -
Frontiers in Pediatrics 2023To investigate the association between Kallikrein-related peptidase-4 (KLK4) rs2235091 polymorphism and susceptibility to dental caries (DC) by a method of systematic... (Review)
Review
OBJECTIVE
To investigate the association between Kallikrein-related peptidase-4 (KLK4) rs2235091 polymorphism and susceptibility to dental caries (DC) by a method of systematic review and meta-analysis.
METHODS
Four English databases were searched for studies on the correlation between KLK4 rs2235091 polymorphism and susceptibility to DC from inception to April 1, 2023. Data analysis was processed by Stata 15.0 software.
RESULTS
Four articles were eligible, including 848 individuals with caries and 463 controls. The results of pooled analysis showed no significant differences in the five gene models (G vs. A: odds ratio (OR) = 1.14, 95% CI: 0.73-1.79, = 0.567; GG + GA vs. AA: OR = 1.01, 95% CI: 0.77-1.32, = 0.489; GG vs. GA + AA: OR = 0.84, 95% CI: 0.57-1.23, = 0.368; GA vs. AA: OR = 1.06, 95% CI: 0.80-1.41, = 0.681; GG vs. AA: OR = 1.15, 95% CI: 0.57-2.31, = 0.690). However, subgroup analysis indicated a statistically significant difference in the dominant (GG + GA vs. AA: OR = 1.74, 95% CI: 1.02-2.96, = 0.042) gene model in primary dentition, but no significance in allelic, recessive, homozygous and heterozygous models. Besides, in permanent dentition, no significant differences were found among the five genetic models (all > 0.05).
CONCLUSION
KLK4 rs2235091 polymorphism may be associated with susceptibility to DC of pediatric primary dentition, but not with the risk of caries of permanent dentition. Genotype GG + GA may increase susceptibility to DC of pediatric primary dentition. However, considering the limited records enrolled in this review, more trials with larger sample sizes and more rigorous designs are needed to verify the conclusions of this meta-analysis in the future.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier INPLASY202380014.
PubMed: 37711595
DOI: 10.3389/fped.2023.1236000