scholarly journals Influence of interleukin-18 polymorphisms on kidney transplantation outcomes: a meta-analysis

2019 ◽  
Author(s):  
Thanee Eiamsitrakoon ◽  
Phuntila Tharabenjasin ◽  
Noel Pabalan ◽  
Rungrawee Mongkolrob ◽  
Aporn Bualuang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Allograft Rejection ◽  
Meta Analysis ◽  
Adverse Outcomes ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Interleukin 18 ◽  
Allograft Survival ◽  
Codominant Model

Abstract Objective: Kidney transplantation (KT) procedures are confronted with adverse outcomes that include allograft failure. Allograft survival are in large part attributed to genetics, which render the recipient susceptible or protected from allograft rejection. The genetics of KT outcomes point to single nucleotide polymorphisms (SNPs) where studies have reported the role of cytokines in allograft survival, one of which is interleukin-18 (IL-18). Reported associations of IL-18 with KT outcomes have been inconsistent. This prompted a meta-analysis to obtain more precise estimates. Methods: From four included articles, we posed two hypotheses about IL-18 SNPs: (1) they are either high in patients (hp) /controls (hc) based on genotype distribution (GD) and (2) they either increase or decrease the risks of allograft rejection. To this end, we compared the IL-18 genotypes to estimate odds ratios [ORs] and 95% confidence intervals using standard genetic models (homozygous, recessive, dominant and codominant). Subgrouping was ethnicity-based. Heterogeneous (random-effects) associations were subjected to outlier treatment which split the outcomes as pre- (PRO) and post- (PSO) outlier. Stability and robustness of the outcomes were analyzed by Bonferroni-correction and sensitivity treatment, respectively.Results: Our results revealed two core outcomes based on significance (Pa < 0.05): (1) genotype frequency was hp than hc (OR 1.34, Pa = 0.0007) in the codominant model (PSO) based on stability and robustness and (2) protection from allograft rejection (OR 0.74, Pa = 0.04) in the dominant model (PRO) based on homogeneity. Subgroup analysis showed that Caucasian and Asian outcomes validated the GD and allograft outcomes, respectively. Conclusions: The IL-18 SNPs showed associations (hp) with KT up to 1.3-fold and protected KT recipients from allograft rejection (26%). Subgroup outcomes delineated the Asian and Caucasian effects. Enabled by outlier treatment, these findings were supported by non-heterogeneity. More studies should confirm or counter our findings.

scholarly journals Influence of interleukin-18 polymorphisms on kidney transplantation outcomes: A meta-analysis

2020 ◽  
Author(s):  
Thanee Einsamtrakoon ◽  
Phuntila Tharabenjasin ◽  
Noel Pabalan ◽  
Adis Tasanarong
Keyword(s):  
Kidney Transplantation ◽  
Allograft Rejection ◽  
Meta Analysis ◽  
Genotype Distribution ◽  
Distribution Analysis ◽  
Nucleotide Polymorphisms ◽  
Interleukin 18 ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Core Outcomes

Aim: Allograft survival post-kidney transplantation (KT) are in large part attributed to genetics, which render the recipient susceptible or protected from allograft rejection. KT studies involving single nucleotide polymorphisms (SNPs) have reported the association of interleukin-18 (IL-18) with KT and its role in allograft rejection. However, the reported outcomes been inconsistent, prompting a meta-analysis to obtain more precise estimates. Methods: We posed two hypotheses about the IL-18 SNPs: their association with KT (H1), and increase or decrease in the risks of allograft rejection (H2). Using standard genetic models, we estimated odds ratios [ORs] and 95% confidence intervals by comparing the IL-18 genotypes between two groups: (i) patients and controls for H1 (GD: genotype distribution analysis); (ii) rejectors and non- rejectors for H2 (allograft analysis). Multiple comparisons were corrected with the Holm-Bonferroni (HB) test. Subgrouping was ethnicity-based (Asians and Caucasians). Heterogeneity was outlier-treated and robustness of outcomes was sensitivity-treated. Results: This meta-analysis generated eight significant outcomes, which HB filtered into four core outcomes, found in the dominant/codominant models. Two of the four were in GD, indicating associations of the IL-18 SNPs with KT (ORs 1.34 to 1.39, 95% CIs 1.13-1.70, PHB = .0007-.004). The other two were in allograft analysis indicating reduced risk with HB P-values of .03 for overall (OR 0.74, 95% CI 0.56-0.93) and Asian (OR 0.70, 95% CI 0.53-0.92). In contrast to the protected Asian subgroup, Caucasians showed non-significant increased risk (OR 1.20. 95% CI .82-1.75, Pa = .35). Sensitivity treatment conferred robustness to all the core outcomes. Conclusions: Overall association of IL-18 SNPs with KT was significant (up to 1.4-fold) and Asians KT recipients were protected (up to 30%). Enabled by outlier treatment, these findings were supported by non-heterogeneity and robustness. More studies may confirm or modify our findings.

scholarly journals Influence of polymorphisms in the vascular endothelial growth factor gene on allograft rejection after kidney transplantation: a meta-analysis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 90
Author(s):  
Thanee Eiamsitrakoon ◽  
Phuntila Tharabenjasin ◽  
Noel Pabalan ◽  
Hamdi Jarjanazi ◽  
Adis Tasanarong
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Meta Analysis ◽  
Clinical Genetics ◽  
Nucleotide Polymorphisms ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
Bonferroni Test

Background: Reported associations of allograft rejection in kidney transplant patients with VEGF single nucleotide polymorphisms (SNPs) have been inconsistent between studies, which prompted a meta-analysis to obtain more precise estimates. Methods: Using the PICO elements, kidney transplant patients (P) were compared by genotype data between rejectors (I) and non-rejectors (C) in order to determine the risk of allograft rejection (O) attributed to the VEGF SNPs. Literature search of four databases yielded seven articles. To calculate risks for allograft rejection, four SNPs were examined. Using the allele-genotype model we compared the variant (var) with the wild-type (wt) and heterozygous (var-wt) alleles. Meta-analysis treatments included outlier and subgroup analyses, the latter was based on ethnicity (Indians/Caucasians) and rejection type (acute/chronic). Multiple comparisons were corrected with the Bonferroni test. Results: Five highly significant outcomes (Pa < 0.01) survived Bonferroni correction, one of which showed reduced risk for the var allele (OR 0.61, 95% CI 0.45-0.82). The remaining four indicated increased risk for the wt allele where the chronic rejection (OR 2.10, 95% CI 1.36-3.24) and Indian (OR 1.44, 95% CI 1.13-1.84) subgroups were accorded susceptibility status. Conclusions: Risk associations for renal allograft rejection were increased and reduced on account of the wt and var alleles, respectively. These findings could render the VEGF polymorphisms useful in the clinical genetics of kidney transplantation.

scholarly journals Association Between Apical Periodontitis and TNF-α -308 G>A Gene Polymorphism: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 28 (5) ◽  
pp. 535-542 ◽  
Author(s):  
Alessandro Guimarães Salles ◽  
Lívia Azeredo Alves Antunes ◽  
Patrícia Arriaga Carvalho ◽  
Erika Calvano Küchler ◽  
Leonardo Santos Antunes
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Apical Periodontitis ◽  
Permanent Teeth ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Eligibility Criteria ◽  
Single Nucleotide ◽  
Mesh Terms ◽  
Tnf Α

Abstract Currently, investigations have focused on the identification of Single Nucleotide Polymorphisms (SNP) involved in host response and its ability to generate an immunity deficiency. The aim of this study was to perform a systematic review (SR) and meta-analysis to evaluate the association between TNF-α -308 G>A polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms “Periapical Periodontitis,” “Periapical Abscess,” “Polymorphism, Genetic,” and “Polymorphism, Single Nucleotide” were used. MeSH synonyms, related terms, and free terms were included. Clinical investigations of individuals with different AP phenotypes in permanent teeth were selected. After application of the eligibility criteria, selected studies were qualified by assessing their methodological quality. A fixed effect model was used for the meta-analysis. The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, two were eligible for quality assessment and were classified as being of moderate evidence. The included studies did not demonstrate association between AP and TNF-α -308 G>A SNP. However, the meta-analysis demonstrated an association between the genotype distribution and AP phenotype (OR= 0.49; confidence interval= 0.25, 0.96; p=0.04). The role of TNF-α -308 G>A SNP in AP phenotypes is debatable. Further studies are needed to confirm and understand the underlying mechanisms of the identified association.

scholarly journals Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hwa Chia Chai ◽  
Kek Heng Chua ◽  
Soo Kun Lim ◽  
Maude Elvira Phipps
Keyword(s):  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Signalling Pathways ◽  
Type I ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Interferon Signalling

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms withinTNFAIP3,STAT4,andIRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles ofSTAT4rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P=0.028, odds ratio(OR)=1.42;P=0.035,OR=1.80, respectively). Polymorphisms inTNFAIP3andIRF5did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated thatSTAT4rs10168266 was significantly associated with the Malaysian SLE as a whole (P=0.014;OR=1.435). The meta-analysis ofSTAT4rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 andPvalue of <0.001.

scholarly journals SNP rs2073618 of the Osteoprotegerin Gene Is Associated with Diabetic Retinopathy in Slovenian Patients with Type 2 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Sara Mankoč Ramuš ◽  
Tina Kumše ◽  
Mojca Globočnik Petrovič ◽  
Daniel Petrovič ◽  
Ines Cilenšek
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Strong Association ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Regulatory Molecule ◽  
Codominant Model ◽  
Osteoprotegerin Gene

Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26–5.13, ). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR.

scholarly journals The role of single nucleotide polymorphisms of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) on susceptibility to herniated nucleus pulposus

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 419
Author(s):  
Azharuddin Azharuddin ◽  
Muhammad Ilmawan ◽  
Jonny Karunia Fajar ◽  
Marhami Fahriani ◽  
Sukamto S. Mamada ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleus Pulposus ◽  
Meta Analysis ◽  
Interleukin 1 ◽  
Recessive Model ◽  
Nucleotide Polymorphisms ◽  
Necrosis Factor Alpha ◽  
Single Nucleotide ◽  
Herniated Nucleus Pulposus

Background: The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL-1A), tumor necrosis factor-alpha (TNF-A), and vitamin D receptor (VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test and presented as odd ratio (OR) and 95% confidence intervals (95%CI). Results: We screened 3,067 unique studies for eligibility and three, two and nine studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

scholarly journals The role of bariatric surgery on kidney transplantation: A systematic review and meta-analysis

2021 ◽  
Vol 15 (10) ◽  
Author(s):  
Yung Lee ◽  
Luschman Raveendran ◽  
Olivia Lovrics ◽  
Chenchen Tian ◽  
Adree Khondker ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bariatric Surgery ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Severe Obesity ◽  
Meta Analysis ◽  
Weighted Mean ◽  
Safety And Efficacy ◽  
Baseline Bmi

Introduction: Obesity (body mass index [BMI] >35 kg/m2) remains a relative contraindication for kidney transplant, while patients after kidney transplantation (KTX) are predisposed to obesity. The present study aims to investigate the role of bariatric surgery in improving transplant candidacy in patients prior to KTX, as well its safety and efficacy in KTX patients postoperatively. Methods: A systematic search was conducted up to March 2020. Both comparative and non-comparative studies investigating the role of bariatric surgery before or after KTX were considered. Outcomes included change in BMI, rates of mortality and complications, and the rate of patients who underwent KTX following bariatric surgery. Pooled estimates were calculated using the random effects meta-analysis of proportions. Results: Twenty-one studies were eligible for final review; 11 studies investigated the role of bariatric surgery before KTX. The weighted mean BMI was 43.4 (5.7) kg/m2 at baseline and 33.9 (6.3) kg/m2 at 29.1 months followup. After bariatric surgery, 83% (95% confidence interval [CI] 57–99) were successfully listed for KTX and 83% (95% CI 65–97) patients subsequently received successful KTX. Ten studies investigated the role of bariatric surgery after kidney transplant. Weighted mean baseline BMI was 43.8 (2.2) kg/m2 and mean BMI at 19.5 months followup was 34.2 (6.7) kg/m2. Overall, all-cause 30-day mortality was 0.5% for both those who underwent bariatric surgery before or after receiving a KTX. The results of this study are limited by the inclusion of only non-randomized studies, limited followup, and high heterogeneity. Conclusions: Bariatric surgery may be safe and effective in reducing weight to improve KTX candidacy in patients with severe obesity and can also be used safely following KTX.

scholarly journals The Association Between Vitamin D and Acute Rejection in Human Kidney Transplantation: A Systematic Review and Meta-analysis Study

2021 ◽  
Author(s):  
Mohammad Mirzakhani ◽  
Sheyda Mohammadkhani ◽  
Shirin Hekmatirad ◽  
Soudabeh Aghapour ◽  
Negar Gorjizadeh ◽  
...  
Keyword(s):  
Vitamin D ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Web Of Science ◽  
Meta Analysis ◽  
Human Kidney ◽  
Before And After ◽  
And Gender ◽  
Role Of It

Abstract Background: Vitamin D (VitD) deficiency is associated with several diseases such as multiple sclerosis, rheumatoid arthritis, respiratory infection, and so forth. In the field of transplantation (kidney transplantation), some studies reported that patients with VitD deficiency are of increased chance of acute rejection, but other studies did not show such a chance. On the other hand, since VitD is a modulatory factor and can reduce the inflammatory response, understanding the exact role of it in transplantation may contribute to tolerance condition in these patients.Methods: The electronic databases, including PubMed, Scopus, Embase, ProQuest, Web of Science, and Google Scholar, were searched for eligible studies. In general, 14 studies with a total of 4,770 patients were included in this meta-analysis. Regarding the methodological heterogeneity, we selected a random-effects combination model. Moreover, OR was chosen as an effect size for this study.Results: After the combination of 14 studies, we showed that patients in the VitD-deficient group had an 82% increased chance of acute rejection compared with patients in the VitD-sufficient group, and this effect was significant (OR 1.82; 95% confidence interval [CI] [1.29, 2.56]; I2 = 52.3%). This result was significant, and, regarding the narrow CI, it can be a conclusive result. Study quality and gender variables were the main sources of inconsistent results in the primary studies. Moreover, using meta-regression, we showed that VitD deficiency (independent from the estimated glomerular filtration rate (eGFR) of patients) increased the chance of acute rejection.Conclusion: The normal VitD status of patients a few days before and after transplantation can reduce the risk of acute rejection, as it has definite modulatory effects on immune cells.

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