Interleukin-10-1082 G/a polymorphism and acute renal graft rejection: a meta-analysis

Figures & data

Figure 1. Flow diagram of trial selection process.

Table 1. Characteristics of the studies included in the meta-analysis.

					AR		Non-AR		AR		Non-AR
Author (Year), Ref.	Country	Ethnicity	Age (years) AR/non-AR	Male (%)	GG	GA + AA	GG	GA + AA	G	A	G	A	Donor type	AR definition	HWE
Chen (2014)11	Netherlands	Caucasian	50.8/48.4	61.8	14	36	63	212	53	47	246	304	Living/deceased	Biopsy	No
Gaafar (2014)12	Saudi Arabia	NI	34/40.5	60.9	5	12	14	61	20	14	63	87	Living	Clinical and biopsy	No
Dhaouadi (2013)13	Tunisia	NI	NI	62.3	16	64	29	122	67	93	130	172	Living/deceased	Histological findings	NI
Mandegary (2013)14	Iran	NI	32/41	62	4	7	42	47	NI				Living	Serum creatinine	NI
Seyhun (2012)15	Turkey	NI	31.2/31.3	61.1	2	17	8	63	12	26	44	98	Living	Clinical and biopsy	NI
Kocierz (2011)16	Poland	Caucasian	40/40	62.3	41	102	2	54	135	151	53	69	Deceased	Clinical and biopsy	No
Azarpira (2009)17	Iran	NI	32.8/31.1	47	2	44	0	54	45	47	50	58	Living/deceased	Clinical or biopsy	Yes
Grinyó (2008)18	Spain	Caucasian	NI	63.6	13	99	33	75	51	71	146	172	Living/deceased	Biopsy	No
Manchanda (2008)19	India	NI	34.8/34.9	84	9	9	41	41	20	16	98	66	Living	Biopsy	NI
Breulmann (2007)20	Germany	NI	NI	59.2	31	83	20	90	NI				Living/deceased	Biopsy	No
Canossi (2007)21	Italy	NI	NI	NI	8	17	12	49	27	23	46	76	Deceased	Biopsy	No
Tajik (2006)22	Iran	NI	NI	69	3	8	4	27	11	11	27	35	Living	Clinical	NI
Gendzekhadze (2006)23	Venezuela	NI	40/40	58.7	2	28	1	32	12	48	16	50	Living/deceased	Serum creatinine  or biopsy	No
Dmitrienko (2005)24	Canada	Caucasian	45/43	57	14	36	19	31	48	52	58	42	Living/deceased	Biopsy	No
Ligeiro (2004)25	Portugal	NI	NI	NI	4	27	5	30	26	36	29	41	Deceased	Biopsy	NI
Plothow (2003)26	Brazil	Caucasian	34.5/34.5	53.8	4	35	3	23	26	52	17	35	Living/deceased	Biopsy	No
Hutchings 1 (2002)27	USA	Caucasian	23/23	76	2	22	4	22	19	29	21	31	Living/deceased	Biopsy	NI
Hutchings 2 (2002)27	USA	African–American	25.6/25.6	70.6	2	15	4	30	18	16	21	47	Living/deceased	Biopsy	NI
Cartwright (2001)28	UK	NI	NI	NI	9	16	8	16	30	20	28	20	Deceased	Biopsy	NI
George (2001)29	UK	NI	NI	NI	5	29	18	53	23	45	73	69	Living/deceased	Serum creatinine  and biopsy	NI
Marshall (2000)30	UK	NI	NI	NI	43	71	33	62	130	98	111	79	Deceased	Serum creatinine and biopsy	NI
Hahn (2000)31	USA	Caucasian	36.7/36.7	65	6	26	24	57	26	38	76	86	Living/deceased	Biopsy	NI
Pelletier (2000)32	UK	Caucasian/  African-American	45.9/45.9	62.4	9	23	12	55	32	32	53	81	Living/deceased	Biopsy	No

Notes: NI, not informed; AR, acute rejection; HWE, Hardy–Weinberg equilibrium.

Figure 2. Odds ratios and 95% CI of individual studies and pooled data for the association between interleukin-10–1082 GG genotype and acute rejection risk in renal transplant recipients.

Figure 3. Odds ratios and 95% CI of individual studies and pooled data for the association between interleukin-10–1082 G allele and acute rejection risk in renal transplant recipients.

Table 2. Subgroup analyses for the primary outcome measurement.

Outcome	Subgroup	No. of studies	OR (95% CI)	p	I^2 (%)
Association between IL-10-1082  GG genotype and AR risk	Caucasian	7	0.88 (0.41–1.89)	0.74	74.6
	Non-Caucasian	16	1.23 (0.96–1.59)	0.11	0
	Europe	10	1.21 (0.73–2.00)	0.46	68.6
	America	6	0.68 (0.40–1.16)	0.16	0
	Asia	6	1.23 (0.70–2.18)	0.47	0
	Africa	1	1.05 (0.53–2.08)	0.89	0
	Living donor	5	1.16 (0.65–2.08)	0.61	0
	Deceased donor	5	1.71 (0.82–3.58)	0.15	58.2
	Living or deceased donor	13	0.88 (0.60–1.30)	0.53	43.9
	Biopsy	21	1.07 (0.79–1.45)	0.66	43
	Non-biopsy	2	1.14 (0.30–4.31)	0.85	37.6
	No deviations from HWE	10	1.34 (0.76–2.36)	0.32	69.3
	Deviations from HWE	1	6.12 (0.29–130.87)	0.25	0
	Not informed	12	0.93 (0.69–1.25)	0.63	0
	Association between IL-10-1082  G allele and AR risk	Caucasian	7	0.95 (0.78–1.16)	0.65	0
Non-Caucasian		14	1.07 (0.91–1.26)	0.42	33.2
Europe		9	1.04 (0.87–1.23)	0.69	43.7
America		6	0.92 (0.69–1.22)	0.54	31.1
Asia		5	1.17 (0.85–1.62)	0.33	0
Africa		1	0.95 (0.65–1.40)	0.81	0
Living donor		4	1.21 (0.81–1.79)	0.35	0
Deceased donor		5	1.07 (0.85–1.36)	0.56	0
Living or deceased donor		12	0.97 (0.83–1.14)	0.73	39.6
Biopsy		20	1.02 (0.90–1.15)	0.79	25.4
Non-biopsy		1	1.30 (0.49–3.44)	0.6	0
No deviations from HWE		9	1.11 (0.93–1.33)	0.26	37.5
Deviations from HWE		1	1.11 (0.64–1.94)	0.71	0
Not informed		11	0.93 (0.78–1.12)	0.44	9.5

Figure 4. Funnel plot showing publication bias for the primary study ends of the association between interleukin-10–1082 GG genotype and acute rejection risk (A) and the association between interleukin-10–1082 G allele and acute rejection risk (B). Note: OR, odds ratios.

Chen Z, Bouamar R, Van Schaik RH, et al. Genetic polymorphisms in IL-2, IL-10, TGF-β1, and IL-2RB and acute rejection in renal transplant patients. Clin Transplant. 2014;28:649–655

 PubMed Web of Science ®Google Scholar

Gaafar A, Iqniebi A, Sheereen A, et al. Study of the cytokine polymorphisms in correlation to rejection and graft survival in renal allograft donors and recipients from a homogenous Saudi population. Transpl Immunol. 2014;30:34–39

 PubMed Web of Science ®Google Scholar

Dhaouadi T, Sfar I, Bardi R, et al. Cytokine gene polymorphisms in kidney transplantation. Transplant Proc. 2013;45:2152–2157

 PubMed Web of Science ®Google Scholar

Mandegary A, Azmandian J, Soleymani S, et al. Effect of donor tumor necrosis factor-alpha and interleukin-10 genotypes on delayed graft function and acute rejection in kidney transplantation. Iran J Kidney Dis. 2013;7:135–141

 PubMed Web of Science ®Google Scholar

Seyhun Y, Mytilineos J, Turkmen A, et al. Influence of cytokine gene polymorphisms on graft rejection in Turkish patients with renal transplants from living related donors. Transplant Proc. 2012;44:1670–1678

 PubMed Web of Science ®Google Scholar

Kocierz M, Siekiera U, Kolonko A, et al. -174G/C interleukin-6 gene polymorphism and the risk of transplanted kidney failure or graft loss during a 5-year follow-up period. Tissue Antigens. 2011;77:283–290

 PubMed Web of Science ®Google Scholar

Azarpira N, Aghdai MH, Raisjalali GA, et al. Influence of recipient and donor IL-10, TNFA and INFG genotypes on the incidence of acute renal allograft rejection. Mol Biol Rep. 2009;36:1621–1626

 PubMed Web of Science ®Google Scholar

Grinyó J, Vanrenterghem Y, Nashan B, et al. Association of four DNA polymorphisms with acute rejection after kidney transplantation. Transpl Int. 2008;21:879–891

 PubMed Web of Science ®Google Scholar

Manchanda PK, Mittal RD. Analysis of cytokine gene polymorphisms in recipient's matched with living donors on acute rejection after renal transplantation. Mol Cell Biochem. 2008;311:57–65

 PubMed Web of Science ®Google Scholar

Breulmann B, Bantis C, Siekierka M, et al. Influence of cytokine genes polymorphisms on long-term outcome in renal transplantation. Clin Transplant. 2007;21:615–621

 PubMed Web of Science ®Google Scholar

Canossi A, Piazza A, Poggi E, et al. Renal allograft immune response is influenced by patient and donor cytokine genotypes. Transplant Proc. 2007;39:1805–1812

 PubMed Web of Science ®Google Scholar

Tajik N, Kazemi T, Delbandi A, et al. The predictive value of HLA-DR matching and cytokine gene polymorphisms in renal allograft acute rejection: A living-unrelated donor (LURD) study. Iran J Immunol. 2006;3:150–156

 PubMedGoogle Scholar

Gendzekhadze K, Rivas-Vetencourt P, Montano RF. Risk of adverse post-transplant events after kidney allograft transplantation as predicted by CTLA-4 + 49 and TNF-alpha -308 single nucleotide polymorphisms: a preliminary study. Transpl Immunol. 2006;16:194–199

 PubMed Web of Science ®Google Scholar

Dmitrienko S, Hoar DI, Balshaw R, Keown PA. Immune response gene polymorphisms in renal transplant recipients. Transplantation. 2005;80:1773–1782

 PubMed Web of Science ®Google Scholar

Ligeiro D, Sancho MR, Papoila A, et al. Impact of donor and recipient cytokine genotypes on renal allograft outcome. Transplant Proc. 2004;36:827–829

 PubMed Web of Science ®Google Scholar

Plothow A, Bicalho MG, Benvenutti R, Contieri FL. Interleukin-10 and acute rejection in renal transplantation. Transplant Proc. 2003;35:1338–1340

 PubMed Web of Science ®Google Scholar

Hutchings A, Guay-Woodford L, Thomas JM, et al. Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients. Pediatr Transplan. 2002;6:69–77

 PubMed Web of Science ®Google Scholar

Cartwright NH, Keen LJ, Demaine AG, et al. A study of cytokine gene polymorphisms and protein secretion in renal transplantation. Transpl Immunol. 2001;8:237–244

 PubMed Web of Science ®Google Scholar

George S, Turner D, Reynard M, et al. Significance of cytokine gene polymorphism in renal transplantation. Transplant Proc. 2001;33:483–484

 PubMed Web of Science ®Google Scholar

Marshall SE, McLaren AJ, Haldar NA, et al. The impact of recipient cytokine genotype on acute rejection after renal transplantation. Transplantation. 2000;70:1485–1491

 PubMed Web of Science ®Google Scholar

Hahn AB, Kasten-Jolly JC, Constantino DM, et al. TNF-alpha, IL-6, IFN-gamma, and IL-10 gene expression polymorphisms and the IL-4 receptor alpha-chain variant Q576R: effects on renal allograft outcome. Transplantation. 2001;72:660–665

 PubMed Web of Science ®Google Scholar

Pelletier R, Pravica V, Perrey C, et al. Evidence for a genetic predisposition towards acute rejection after kidney and simultaneous kidney-pancreas transplantation. Transplantation. 2000;70:674–680

 PubMed Web of Science ®Google Scholar