Blood Res 2021; 56(1):
Published online March 31, 2021
https://doi.org/10.5045/br.2021.2020201
© The Korean Society of Hematology
Correspondence to : Mohammad Ahmadvand, Ph.D.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Dameshq St, Tehran P.O. Box: 1411713135 (M.A.), Tehran, Iran
E-mail: Mahmadvand@sina.tums.ac.ir
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The association between the risk of allograft rejection after organ transplantation and FAS gene polymorphism has been evaluated previously. However, inconsistent results have been reported. Hence, we conducted the most up-to-date meta-analysis to evaluate this association. All eligible studies reporting the association between FAS-670A>G polymorphism and the risk of allograft rejection published up to December 2019 were extracted using a comprehensive systematic database search in the Web of Science, Scopus, and PubMed. The pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated to determine the association strength. This meta-analysis included six case-control studies with 277 patients who experienced allograft rejection and 1,001 patients who did not experience allograft rejection (controls) after organ transplantation. The overall results showed no significant association between FAS-670A>G polymorphism and the risk of allograft rejection in five genetic models (dominant model: OR=0.81, 95% CI=0.58‒1.12; recessive model: OR=0.10, 95% CI=0.80‒1.53; allelic model: OR=0.96, 95% CI=0.79‒1.18; GG vs. AA: OR=0.92, 95% CI=0.62‒1.36; and AG vs. AA: OR=0.75, 95% CI=0.52‒1.08). Moreover, subgroup analysis according to ethnicity and age did not reveal statistically significant results. Our findings suggest that FAS-670A>G polymorphism is not associated with the risk of allograft rejection after organ transplantation.
Keywords FAS, Allograft rejection, Polymorphism, Meta-analysis
Blood Res 2021; 56(1): 17-25
Published online March 31, 2021 https://doi.org/10.5045/br.2021.2020201
Copyright © The Korean Society of Hematology.
Mohammad Masoud Eslami1, Ramazan Rezaei2, Sara Abdollahi3, Afshin Davari4, Mohammad Ahmadvand5
1Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, 2Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, 3Mazandaran Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, 4Department of Medical Parasitology and Mycology, School of Public Health, 5Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
Correspondence to:Mohammad Ahmadvand, Ph.D.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Dameshq St, Tehran P.O. Box: 1411713135 (M.A.), Tehran, Iran
E-mail: Mahmadvand@sina.tums.ac.ir
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The association between the risk of allograft rejection after organ transplantation and FAS gene polymorphism has been evaluated previously. However, inconsistent results have been reported. Hence, we conducted the most up-to-date meta-analysis to evaluate this association. All eligible studies reporting the association between FAS-670A>G polymorphism and the risk of allograft rejection published up to December 2019 were extracted using a comprehensive systematic database search in the Web of Science, Scopus, and PubMed. The pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated to determine the association strength. This meta-analysis included six case-control studies with 277 patients who experienced allograft rejection and 1,001 patients who did not experience allograft rejection (controls) after organ transplantation. The overall results showed no significant association between FAS-670A>G polymorphism and the risk of allograft rejection in five genetic models (dominant model: OR=0.81, 95% CI=0.58‒1.12; recessive model: OR=0.10, 95% CI=0.80‒1.53; allelic model: OR=0.96, 95% CI=0.79‒1.18; GG vs. AA: OR=0.92, 95% CI=0.62‒1.36; and AG vs. AA: OR=0.75, 95% CI=0.52‒1.08). Moreover, subgroup analysis according to ethnicity and age did not reveal statistically significant results. Our findings suggest that FAS-670A>G polymorphism is not associated with the risk of allograft rejection after organ transplantation.
Keywords: FAS, Allograft rejection, Polymorphism, Meta-analysis
Table 1 . Characteristics of studies included in meta-analysis of overall FAS-670A>G..
Study author | Year | Country | Ethnicity | Sex cases/controls | Total cases/control | Age case/control (mean) | Genotyping method | Quality score |
---|---|---|---|---|---|---|---|---|
Cappellesso | 2002 | France | Caucasian | M=NR | 20/77 | NR/NR | RFLP-PCR | 6 |
F=NR | ||||||||
Marín | 2006 | Spain | Caucasian | M=NR | 53/227 | 49±12/NR | RFLP-PCR | 7 |
F=NR | ||||||||
Jahadi Hosseini | 2009 | Iran | Caucasian | M=NR | 47/225 | 43.67±22.18/40.08±22.18 | ASO-PCR | 7 |
F=NR | ||||||||
Ertan | 2010 | Turkey | Caucasian | M=NR | 16/37 | 12.3±0.6/12.3±0.6 | RFLP-PCR | 7 |
F=NR | ||||||||
Girnita | 2011 | Multicenter | Mixed | M=NR | 124/405 | NR/NR | PCR | 6 |
F=NR | ||||||||
Fadel | 2016 | Egypt | Arab | M=10/19 | 17/30 | 9.37±3.56/10.09±2.95 | RFLP-PCR | 8 |
F=7/11 |
Abbreviations: F, female; M, male; NR, not reported..
Table 2 . Distribution of genotype and allele among FAS 670A/G patients and controls..
Study author | Rejection cases | Non-rejection control | MAF | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AA | AG | GG | A | G | AA | AG | GG | A | G | ||||
Cappellesso | 8 | 9 | 3 | 25 | 15 | 25 | 40 | 12 | 90 | 64 | 0/54 | 0/415 | |
Marín | 15 | 24 | 14 | 54 | 52 | 65 | 106 | 56 | 236 | 218 | 0/33 | 0/48 | |
Jahadi Hosseini | 12 | 20 | 15 | 44 | 50 | 77 | 73 | 75 | 227 | 223 | ≤0.001 | 0/495 | |
Ertan | 4 | 10 | 2 | 18 | 14 | 11 | 23 | 3 | 45 | 29 | 0/06 | 0/391 | |
Girnita | 40 | 46 | 38 | 126 | 122 | 81 | 213 | 111 | 375 | 435 | 0/24 | 0/537 | |
Fadel | 4 | 3 | 10 | 11 | 23 | 11 | 3 | 16 | 25 | 35 | ≤0.001 | 0/583 |
Abbreviations: MAF, minor allele frequency of the control group;
Table 3 . Main results of pooled OR in meta-analysis of FAS 670A/G gene polymorphisms..
Genetic model | Sample size | Test of association | Test of heterogeneity | Test of publication bias (Begg’s test) | Test of publication bias (Egger’s test) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Case/control | OR | 95% CI (P) | I2 (%) | Z | T | |||||||||
Overall population | Dominant model | 277/1001 | 0.81 | 0.58–1.12 (0.19) | 33.2 | 0.18 | 0.94 | 0.34 | 1.8 | 0.14 | ||||
Recessive model | 277/1001 | 1.10 | 0.80–1.53 (0.55) | 0 | 0.99 | 0.19 | 0.85 | 0.14 | 0.89 | |||||
Allelic model | 277/1001 | 0.96 | 0.79–1.18 (0.7) | 0 | 0.74 | 1.69 | 0.09 | 1.81 | 0.14 | |||||
GG vs. AA | 277/1001 | 0.92 | 0.62–1.36 (0.66) | 0 | 0.78 | 0.56 | 0.57 | 1.8 | 0.14 | |||||
AG vs. AA | 277/1001 | 0.75 | 0.52–1.08 (0.12) | 48 | 0.08 | 0.94 | 0.34 | 1.66 | 1.17 | |||||
Subgroup analysis | ||||||||||||||
Caucasians | Dominant model | 136/566 | 1.12 | 0.71–1.78 (0.62) | 0 | 0.74 | 0 | 1 | -0.35 | 0.76 | ||||
Recessive model | 136/566 | 1.02 | 0.63–1.66 (0.93) | 0 | 0.97 | 1.36 | 0.17 | 0.86 | 0.48 | |||||
Allelic model | 136/566 | 1.06 | 0.80–1.41 (0.67) | 0 | 0.91 | 0 | 1 | -0.36 | 0.75 | |||||
GG vs. AA | 136/566 | 1.15 | 0.64–2.06 (0.64) | 0 | 0.94 | 0.68 | 0.49 | 0.05 | 0.96 | |||||
AG vs. AA | 136/566 | 1.15 | 0.70–1.89 (0.58) | 0 | 0.64 | 0 | 1 | -0.38 | 0.74 | |||||
Children | Dominant model | 157/472 | 0.62 | 0.40–1.06 (0.07) | 37.7 | 0.20 | 1.57 | 0.11 | 5.15 | 0.12 | ||||
Recessive model | 157/472 | 1.19 | 0.77–1.84 (0.43) | 0 | 0.96 | 1.57 | 0.11 | 2.79 | 0.21 | |||||
Allelic model | 157/472 | 0.90 | 0.68–1.17 (0.42) | 0 | 0.43 | 1.57 | 0.11 | 4.79 | 0.13 | |||||
GG vs. AA | 157/472 | 0.79 | 0.47–1.33 (0.36) | 0 | 0.48 | 0.52 | 0.60 | 2.29 | 0.21 | |||||
AG vs. AA | 157/472 | 0.72 | 0.27–1.95 (0.52) | 40 | 0.18 | 1.57 | 0.11 | 53.19 | 0.01 | |||||
Adults | Dominant model | 100/452 | 1.22 | 0.72–2.07 (0.47) | 0 | 0.45 | 1.0 | 0.31 | * | * | ||||
Recessive model | 100/452 | 1.01 | 0.60–1.69 (0.98) | 0 | 0.76 | 1.0 | 0.31 | * | * | |||||
Allelic model | 100/452 | 1.09 | 0.79–1.51 (0.60) | 0 | 0.76 | 1.0 | 0.31 | * | * | |||||
GG vs. AA | 100/452 | 1.17 | 0.62–2.22 (0.62) | 0 | 0.79 | 1.0 | 0.31 | * | * | |||||
AG vs. AA | 100/452 | 1.27 | 0.71–2.28 (0.41) | 0 | 0.33 | 1.0 | 0.31 | * | * |
*Was not calculable..
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