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Journal of Lipid Research Oct 2010Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a... (Meta-Analysis)
Meta-Analysis Review
Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p.T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No significant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies (weighted mean age, 46.7 ± 10.5 years; BMI, 23.9 ± 3.5 kg/m(2)). Presence of the minor 632V allele correlated with reduced LDL-C concentrations (n = 367) compared with homozygosity for the 632A variant [n = 614; -0.11 mmol/l (95% CI, range: -0.20 to -0.02 mmol/l); P = 0.01]. The remaining polymorphisms were not associated with plasma lipid levels. Carriers of the 19H allele exhibited lower campesterol/TC (n = 83; P < 0.001), sitosterol/TC (P < 0.00001), and cholestanol/TC (P < 0.00001), and increased lathosterol/TC ratios (P = 0.001) compared with homozygous 19D allele carriers (n = 591). The ABCG8 632V variant was associated with a clinically irrelevant LDL-C reduction, whereas the 19H allele correlated with decreased cholesterol absorption and increased synthesis without affecting the lipid profile. Hence, associations between frequently studied missense ABCG5/G8 polymorphisms and markers of cholesterol homeostasis are modest at best.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Adult; Cholesterol; Genotype; Humans; Hypercholesterolemia; Lipoproteins; Middle Aged; Polymorphism, Genetic
PubMed: 20581104
DOI: 10.1194/jlr.M008128 -
Experimental and Molecular Pathology Feb 2018This review summarizes recent studies on plasma-membrane ecto-ATP synthase from structural and functional standpoints to possible pathophysiological roles. This review... (Review)
Review
This review summarizes recent studies on plasma-membrane ecto-ATP synthase from structural and functional standpoints to possible pathophysiological roles. This review discusses significant new contributions and perspectives in the area of ecto-ATP synthase since the topic was last reviewed in 2015. Following an extensive summary of the cell types in which the ecto-ATP synthase is present, its structural and functional mechanism are discussed and physiological and pathological roles of the ecto-ATP synthase are reviewed and evaluated. Attempts to define the possible role of ecto-ATP synthase as possible target for anti-cancer and anti-obesity interventions are discussed.
Topics: Animals; Cell Membrane; Humans; Proton-Translocating ATPases
PubMed: 29305066
DOI: 10.1016/j.yexmp.2017.12.006 -
The Cochrane Database of Systematic... Oct 2021Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists... (Meta-Analysis)
Meta-Analysis
Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.
BACKGROUND
Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first-line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP-1RA and SGLT2i may exert positive effects on patients with known CVD.
OBJECTIVES
To systematically review the available evidence on the benefits and harms of DPP4i, GLP-1RA, and SGLT2i in people with established CVD, using network meta-analysis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP-1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, all-cause mortality, hospitalisation for heart failure (HF), and safety outcomes.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta-analyses and network meta-analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope.
MAIN RESULTS
We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta-analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP-1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow-up duration. 1. DPP4i versus placebo Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high-certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high-certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high-certainty evidence), and all-cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high-certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate-certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low-certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate-certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate-certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate-certainty evidence). 2. GLP-1RA versus placebo Our findings indicate that GLP-1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high-certainty evidence), all-cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high-certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high-certainty evidence). GLP-1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate-certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high-certainty evidence). GLP-1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low-certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low-certainty evidence). We are uncertain about the effect of GLP-1RA on hypoglycaemia and bone fractures. 3. SGLT2i versus placebo This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate-certainty evidence), all-cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate-certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high-certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high-certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate-certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate-certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate-certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high-certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low-certainty evidence). 4. Network meta-analysis Because we failed to identify direct comparisons between each class of the agents, findings from our network meta-analysis provided limited novel insights. Almost all findings from our network meta-analysis agree with those from the standard meta-analysis. GLP-1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate-certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta-analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all-cause mortality.
AUTHORS' CONCLUSIONS
Findings from both standard and network meta-analyses of moderate- to high-certainty evidence suggest that GLP-1RA and SGLT2i are likely to reduce the risk of CVD mortality and all-cause mortality in people with established CVD; high-certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate-certainty evidence likely supports the use of GLP-1RA to reduce fatal and non-fatal stroke. Future studies conducted in the non-diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose-lowering effects.
Topics: Cardiovascular Diseases; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Glucagon-Like Peptide 1; Glucose; Humans; Network Meta-Analysis; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 34693515
DOI: 10.1002/14651858.CD013650.pub2 -
Expert Opinion on Pharmacotherapy 2023This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2 diabetes mellitus (T2DM).
AREAS COVERED
We examined RCTs with T2DM comparing the clinical effectiveness and safety of 20 mg once daily oral dose of bexagliflozin with placebo for managing glycemia till 28 May 2023, published on databases like ClinicalTrials.gov, PubMed, Embase, and Cochrane Library. Furthermore, reduction of body weight, fasting plasma sugarr(FPG), systolic blood pressure (SBP) and the percentage of individuals who achieved glycated hemoglobin (HbA1c) of < 7% from baseline were also evaluated. The Review Manager 5 was utilized to investigate the retrieved data.
EXPERT OPINION
We involved eight RCTs. Bexagliflozin was significantly superior in reducing HbA1c[least squares mean difference(LSMD) = -0.45,95% confidence interval (CI =-0.55 to -0.34, < 0.00001], FPG [LSMD= -1.37, 95%CI =-1.73 to -1.00, < 0.00001], body weight (LSMD= -1.77, 95%CI =-2.44 to-1.10, < 0.00001), and SBP(LSMD= -4.11,95%CI = -6.18 to -2.03, = 0.0001) in comparison to placebo. The safety outcomes of bexagliflozin were consistent with the placebo arm. This study concluded that bexagliflozin seems to be a promising oral anti-diabetic drug for enhancing glycemic management in adult patients with T2DM.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glycated Hemoglobin; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Body Weight; Glucose; Sodium
PubMed: 37817422
DOI: 10.1080/14656566.2023.2269854 -
Clinical Pharmacokinetics Oct 2021Mycophenolic acid (MPA) is among the most commonly prescribed medications for immunosuppression following organ transplantation. Highly variable MPA exposure and drug... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycophenolic acid (MPA) is among the most commonly prescribed medications for immunosuppression following organ transplantation. Highly variable MPA exposure and drug response are observed among individuals receiving the same dosage of the drug. Identification of candidate genes whose polymorphisms could be used to predict MPA exposure and clinical outcome is of clinical value.
OBJECTIVES
This study aimed to determine the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of MPA in humans by means of a systematic review and meta-analysis.
METHODS
A systematic search was conducted on PubMed, EMBASE, Web of Sciences, Scopus, and the Cochrane Library databases. A meta-analysis was conducted to determine any associations between genetic polymorphisms and pharmacokinetic or pharmacodynamic parameters of MPA. Pooled-effect estimates were calculated by means of the random-effects model.
RESULTS
A total of 37 studies involving 3844 individuals were included in the meta-analysis. Heterozygous carriers of the UGT1A9 -275T>A polymorphism were observed to have a significantly lower MPA exposure than wild-type individuals. Four single nucleotide polymorphisms (SNPs), namely UGT1A9 -2152C>T, UGT1A8 518C>G, UGT2B7 211G>T, and SLCO1B1 521T>C, were also significantly associated with altered MPA pharmacokinetics. However, none of the investigated SNPs, including SNPs in the IMPDH gene, were found to be associated with the clinical efficacy of MPA. The only SNP that was associated with adverse outcomes was SLCO1B3 344T>G.
CONCLUSIONS
The present systematic review and meta-analysis identified six SNPs that were significantly associated with pharmacokinetic variability or adverse effects of MPA. Our findings represent the basis for future research and clinical implications with regard to the role of pharmacogenetics in MPA pharmacokinetics and drug response.
Topics: Area Under Curve; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver-Specific Organic Anion Transporter 1; Mycophenolic Acid; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 34105062
DOI: 10.1007/s40262-021-01037-7 -
Diabetes Research and Clinical Practice Jun 2018A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and moderate renal function impairment: A systematic review and meta-analysis.
AIMS
A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) and moderate renal function impairment.
METHODS
Embase, Medline, and Cochrane Central were searched, and randomized controlled trials comparing SGLT2 inhibitors to placebos and other drugs for T2D were collected.
RESULTS
Seven RCTs with a total of 3307 participants were included, and the overall bias was low. In the patients with T2D and moderate renal function impairment (30 ml/min/1.73 m ≤ estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m) compared with the placebo, SGLT2 inhibitors improved HbA1c significantly (WMD, -0.23%; 95% CI: -0.38 to -0.08), presented a lower incidence of hypoglycemia (30.1% vs. 34.6%; RR, 0.85; 95% CI: 0.76 to 0.96), led to the reduction of eGFR (WMD, -1.74 ml/min/1.73 m; 95% CI: -3.45 to -0.03), resulted in an obvious reduction in body weight (WMD, -1.45 kg; 95% CI: -2.01 to -0.89), and presented a similar risk of urinary tract infection and genital infection.
CONCLUSIONS
SGLT2 inhibitors are safe, but mildly reduce the HbA1c level. The clinical significance of SGLT2 inhibitors in the target population was limited.
Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 29649541
DOI: 10.1016/j.diabres.2018.03.047 -
The World Journal of Biological... Mar 2023This systematic review and meta-analysis focussed on insights into the relationship between -rs1006737 and -rs1344706 polymorphisms and cognitive performance in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This systematic review and meta-analysis focussed on insights into the relationship between -rs1006737 and -rs1344706 polymorphisms and cognitive performance in schizophrenia (SCZ) spectrum and bipolar disorder (BD) and provide some contributions for clinical practice.
METHODS
We searched the websites databases (PubMED, PsycINFO, Web of Science, EMBASE and Cochrane Library) using eligibility and exclusion criteria to capture all potential studies, based on PICO model and according to the PRISMA.
RESULTS
Eight articles were included in this systematic review (five referring to -rs1006737 and three related to -rs1344706 polymorphisms), with a total of 5759 participants (1751 SCZ patients, 348 BD patients, 3626 controls and 34 first-degree relatives). The results demonstrated that the pooled effect of -rs1006737 (risk difference RD = 0.08; 95% CI 0.02-0.15) was associated with altered cognitive function in patients with severe mental disorders, but not Z-rs1344706 polymorphism (RD = 0.19; 95% CI 0.09-0.48.
CONCLUSION
The present meta-analysis provides evidence regarding slight association between -rs1006737 polymorphisms and cognitive performance in severe mental disorders, indicating that cognitive impairment in severe mental disorders associated with the rs1006737 risk variants could only be expressed when interacting with environmental exposures. This study is registered with PROSPERO, number CRD42021246726.
Topics: Humans; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Kruppel-Like Transcription Factors; Schizophrenia; Cognition; Calcium Channels, L-Type
PubMed: 35786202
DOI: 10.1080/15622975.2022.2097308 -
Journal of Neurology Feb 2023Retina thickness has been studied in patients with neuromyelitis optica spectrum disorders (NMOSD) without distinguishing serostatus and limited data are available in... (Meta-Analysis)
Meta-Analysis Review
Retina thickness in clinically affected and unaffected eyes in patients with aquaporin-4 immunoglobulin G antibody seropositive neuromyelitis optica spectrum disorders: a systematic review and meta-analysis.
BACKGROUND AND PURPOSE
Retina thickness has been studied in patients with neuromyelitis optica spectrum disorders (NMOSD) without distinguishing serostatus and limited data are available in unaffected eyes. We aimed to investigate retina thickness in eyes of aquaporin-4 immunoglobulin G antibody seropositive (AQP4-IgG) NMOSD patients with optic neuritis (AQP4-ON) and without (AQP4-NON).
METHODS
Eligible studies were identified by searching PubMed and Embase. Mean difference (MD, μm) with corresponding 95% confidence interval (CI) was pooled with random-effect models. The primary measures were average thickness of peripapillar retinal nerve fiber layer (pRNFL) centered on optic disc and the combination of ganglion cell layer and inner plexiform layer (GCIPL) at macula.
RESULTS
We included 21 studies enrolling 787 AQP4-IgG NMOSD patients. Compared with healthy control, pRNFL was thinner in eyes of AQP4-ON (- 32.78, 95% CI [- 36.24, - 29.33]) and AQP4-NON (- 2.76, 95% CI [- 3.94, - 1.58]), so was GICPL in AQP4-ON (-21.38, 95% CI [- 24.01, - 18.74]) and AQP4-NON (95% CI - 2.96, [- 3.91, - 2.00]). Compared with multiple sclerosis with ON, AQP4-ON had thinner pRNFL (- 13.56, 95%CI [- 16.51, - 10.60]) and GCIPL (- 9.12, 95% CI [- 11.88, - 6.36]). AQP4-ON and myelin oligodendrocyte glycoprotein antibody-associated demyelination with ON (MOG-ON) had similar pRNFL (0.59, 95% CI [- 6.61, 7.79]) and GCIPL thickness (- 0.55, 95% CI [- 2.92, 1.82]). AQP4-NON had similar pRNFL and GCIPL thickness to MOG-NON and multiple sclerosis without ON.
CONCLUSIONS
The average thickness of pRNFL and GICPL decreased both in AQP4-ON and AQP4-NON eyes. AQP4-ON eyes had a similar level of pRNFL and GICPL thinning to MOG-ON eyes, so did AQP4-NON to MOG-NON eyes.
Topics: Humans; Neuromyelitis Optica; Immunoglobulin G; Aquaporin 4; Tomography, Optical Coherence; Retina; Optic Neuritis; Multiple Sclerosis; Autoantibodies; Myelin-Oligodendrocyte Glycoprotein
PubMed: 36355186
DOI: 10.1007/s00415-022-11482-4 -
Sexual Medicine Reviews Oct 2020A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature...
INTRODUCTION
A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature ejaculation (PE); however, the results remain inconclusive.
OBJECTIVES
This systematic review aimed: (i) to determine whether an association exists between gene(s) or allelic variant(s) and PE; (ii) to assess whether the associations are consistent across studies in magnitude and direction, and (iii) to identify any limitation, gap, or shortcoming in the included studies.
METHODS
The literature search was conducted in PubMed, MEDLINE, Scopus, Cochrane Library, EMBASE, Academic Search Complete, Google Scholar, and CINAHL databases.
RESULTS
Different gene variants associated with PE were assessed. 25 genetic association studies met the inclusion criteria that investigated 11 genes, 2,624 men with PE compared with 9,346 men as controls, twins, and siblings. 19 studies demonstrated a significant association with PE, whereas 4 studies denied such a relationship. SLC6A4 gene polymorphism was investigated in 11 studies (7 studies demonstrated a significant relationship with PE, and 4 studies denied such a relationship). Dopamine transporter gene (DAT1) polymorphism was investigated in 4 studies exhibiting a significant relationship. Androgen receptor gene polymorphisms were investigated in 2 studies, 1 with a significant relationship and the other with a non-significant relationship. Oxytocin gene polymorphisms and tryptophan hydroxylase 2 gene polymorphisms were investigated in 2 studies with a significant relationship.
CONCLUSION
While this review has highlighted several genes that may be potentially associated with PE such as SLC6A4, limitations such as variance in study methods, lack of robust findings, small sample sizes, lack of reproducibility, quality of reporting, and quality of assessment remain a major concern. Further efforts such as standardizing reporting, exploring complementary designs, and the use of genome-wide association studies technology are warranted to test the reproducibility of these early findings. Mostafa T, Abdel-Hamid IA, Taymour M, et al. Gene Variants in Premature Ejaculation: Systematic Review and Future Directions. Sex Med Rev 2020;8:586-602.
Topics: Dopamine Plasma Membrane Transport Proteins; Genetic Association Studies; Humans; Male; Oxytocin; Polymorphism, Genetic; Premature Ejaculation; Receptors, Androgen; Receptors, Serotonin; Reproducibility of Results; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase
PubMed: 32800770
DOI: 10.1016/j.sxmr.2020.07.002 -
International Journal of Clinical... 2022The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk.
METHODS
Relevant publications were systematically retrieved from PubMed, EMBASE, and the Cochrane Library up to December 2020. Data from eligible case-control and cohort studies were extracted for qualitative and quantitative analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between gene polymorphisms and PTDM in the quantitative meta-analysis.
RESULTS
A total of 43 eligible articles were identified, and 16 studies on 9 DNA variants from 8 genes were included in the meta-analysis. rs7903146 was significantly associated with PTDM risk in 5 genetic models (OR (95% CI): allelic: 1.59 (1.17-2.16), =0.003; dominant recessive: 1.62 (1.14, 2.31), =0.007; recessive: 1.87 (1.18, 2.94), =0.007; homozygote: 2.21 (1.23, 3.94), =0.008; and heterozygote 1.50 (1.08, 2.10), =0.017). rs2237892 was significantly correlated with PTDM risk in 3 genetic models (allelic: 0.68 (0.58, 0.81), < 0.001; dominant: 0.6 (049, 0.74), < 0.001; and heterozygote: 0.61 (0.48, 0.76), < 0.001). rs5219 was significantly linked with PTDM in the recessive genetic model (1.59 (1.01, 2.50), =0.047). No significant correlations of PTDM with rs12255372, rs13266634, rs1801282, rs10811661, rs1111875, and rs4402960 polymorphisms were found.
CONCLUSIONS
The gene polymorphisms of rs7903146, rs2237892, and rs5219 may predispose kidney transplant recipients to PTDM. Large sample size studies on diverse ethnic populations were warranted to confirm our findings.
Topics: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; KCNQ1 Potassium Channel; Kidney; Polymorphism, Single Nucleotide; RNA-Binding Proteins
PubMed: 35685576
DOI: 10.1155/2022/7140024