FAS-670A＞G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis

Mohammad Masoud Eslami; Ramazan Rezaei; Sara Abdollahi; Afshin Davari; Mohammad Ahmadvand

doi:10.5045/br.2021.2020201

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Blood Res 2021; 56(1):

Published online March 31, 2021

https://doi.org/10.5045/br.2021.2020201

FAS-670A＞G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis

Mohammad Masoud Eslami¹, Ramazan Rezaei², Sara Abdollahi³, Afshin Davari⁴, Mohammad Ahmadvand⁵

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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

Received: August 14, 2020; Revised: December 12, 2020; Accepted: February 23, 2021

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.

Abstract

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Abstract

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

Article

Review Article

Blood Res 2021; 56(1): 17-25

Published online March 31, 2021 https://doi.org/10.5045/br.2021.2020201

FAS-670A＞G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis

Mohammad Masoud Eslami¹, Ramazan Rezaei², Sara Abdollahi³, Afshin Davari⁴, Mohammad Ahmadvand⁵

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

Received: August 14, 2020; Revised: December 12, 2020; Accepted: February 23, 2021

Abstract

Keywords: FAS, Allograft rejection, Polymorphism, Meta-analysis

Abstract

Fig 1.

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Figure 1.Flow diagram of the study selection process.

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

Fig 2.

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Figure 2.Forest plot of the association between FAS-670A>G gene single-nucleotide polymorphism and the risk of allograft rejection in the dominant model.

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

Fig 3.

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Figure 3.Forest plot of the association between FAS-670A>G gene single-nucleotide polymorphism and the risk of allograft rejection in the recessive model.

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

Fig 4.

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Figure 4.Forest plot of the association between FAS-670A>G gene single-nucleotide polymorphism and the risk of allograft rejection in the allelic model.

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

Fig 5.

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Figure 5.Forest plot of the association between FAS-670A>G gene single-nucleotide polymorphism and the risk of allograft rejection in the AG vs. AA model.

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

Fig 6.

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Figure 6.Forest plot of the association between FAS-670A>G gene single-nucleotide polymorphism and the risk of allograft rejection in the GG vs. AA model.

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

Fig 7.

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Figure 7.Sensitivity analysis to investigate whether FAS-670A/G gene single nucleotide polymorphism contributes to risk for allograft rejection (Recessive model).

Blood Research 2021; 56: 17-25https://doi.org/10.5045/br.2021.2020201

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 et al. [24]	2002	France	Caucasian	M=NR	20/77	NR/NR	RFLP-PCR	6
Cappellesso et al. [24]	2002	France	Caucasian	F=NR	20/77	NR/NR	RFLP-PCR	6
Marín et al. [25]	2006	Spain	Caucasian	M=NR	53/227	49±12/NR	RFLP-PCR	7
Marín et al. [25]	2006	Spain	Caucasian	F=NR	53/227	49±12/NR	RFLP-PCR	7
Jahadi Hosseini et al. [26]	2009	Iran	Caucasian	M=NR	47/225	43.67±22.18/40.08±22.18	ASO-PCR	7
Jahadi Hosseini et al. [26]	2009	Iran	Caucasian	F=NR	47/225	43.67±22.18/40.08±22.18	ASO-PCR	7
Ertan et al. [16]	2010	Turkey	Caucasian	M=NR	16/37	12.3±0.6/12.3±0.6	RFLP-PCR	7
Ertan et al. [16]	2010	Turkey	Caucasian	F=NR	16/37	12.3±0.6/12.3±0.6	RFLP-PCR	7
Girnita et al. [27]	2011	Multicenter	Mixed	M=NR	124/405	NR/NR	PCR	6
Girnita et al. [27]	2011	Multicenter	Mixed	F=NR	124/405	NR/NR	PCR	6
Fadel et al. [28]	2016	Egypt	Arab	M=10/19	17/30	9.37±3.56/10.09±2.95	RFLP-PCR	8
Fadel et al. [28]	2016	Egypt	Arab	F=7/11	17/30	9.37±3.56/10.09±2.95	RFLP-PCR	8

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					P-HWE	MAF

	AA	AG	GG	A	G	AA	AG	GG	A	G
Cappellesso et al. [24]	8	9	3	25	15	25	40	12	90	64	0/54	0/415
Marín et al. [25]	15	24	14	54	52	65	106	56	236	218	0/33	0/48
Jahadi Hosseini et al. [26]	12	20	15	44	50	77	73	75	227	223	≤0.001	0/495
Ertan et al. [16]	4	10	2	18	14	11	23	3	45	29	0/06	0/391
Girnita et al. [27]	40	46	38	126	122	81	213	111	375	435	0/24	0/537
Fadel et al. [28]	4	3	10	11	23	11	3	16	25	35	≤0.001	0/583

Abbreviations: MAF, minor allele frequency of the control group; P-HWE, P-value for Hardy–Weinberg equilibrium..

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 (%)	P	Z	P	T	P
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	^*	^*