A deeper understanding of the association between CTLA4 +49A/G and acute rejection in renal transplantation: an updated meta-analysis

Figures & data

Figure 1. Flow diagram of search strategy and study selection.

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

First author	Year	Ethnicity	Polymorphisms	Cases (AR) 481	Controls (Non-AR) 1335	p Value for HWE	Genotyping method
Dmitrenko	2005	European	rs5742909 (−318 C/T), rs231775 (+49 G/A)	50	50	Yes	PCR-RFLP
Wisniewski	2006	European	rs5742909 (−318 C/T), rs231775 (+49G/A)	38	53	Yes	PCR-RFLP
Gorgi	2006	African	rs5742909 (−318 C/T), rs231775 (+49G/A)	31	39	Yes	PCR-RFLP/PCR-SSP
Gendzekhadze	2006	European	rs733618 (−1722T/C), rs4553808 (−1661A/G), rs5742909 (−318 C/T), rs231775 (+49G/A)	30	33	Yes	PCR-RFLP
Haimila	2009	European	rs4553808 (−1661A/G), rs5742909 (−318C/T), rs231775 (+49G/A), rs3087243 (+6230 G/A)	109	546	Yes
Ruhi	2010	European	rs4553808 (−1661A/G), rs5742909 (−318C/T), rs231775 (+49G/A), rs3087243 (+6230 G/A)	49	47	Yes	PCR-RFLP
Kim	2010	Asian	rs5742909 (−318 C/T), rs231775 (+49G/A)	59	266	Yes	PCR
Gao	2012	Asian	rs733618 (−1722T/C), rs4553808 (−1661A/G), rs5742909 (−318C/T), rs231775 (+49G/A), rs3087243 (+6230 G/A)	45	122	Yes	DNA sequencing
Domanski	2012	European	rs231775 (+49G/A)	70	179	Yes	RT-PCR

Notes: PCR, polymerase chain reaction; PCR-RFLP, polymerase chain reaction with restriction fragment length polymorphism; PCR-SSP, polymerase chain reaction with sequence-specific primers; RT-PCR, real-time polymerase chain reaction; LT, liver transplantation; RT, renal transplantation; p_Het; p value for heterogeneity; G, guanine; A, adenine; C, cytosine; T, thymine.

Figure 2. Meta-analysis for the association between AR risk in renal transplantation and CTLA4 +49A/G (GG + AG vs. AA).

Figure 3. Meta-analysis for the association between AR risk in renal transplantation and CTLA4 +49A/G (GG vs. AG + AA).

Figure 4. Meta-analysis for the association between AR risk in renal transplantation and CTLA4 +49A/G (GG vs. AA).

Figure 5. Meta-analysis for the association between AR risk in renal transplantation and the CTLA4 +49A/G (AG vs. AA).

Figure 6. Meta-analysis for the association between AR risk in renal transplantation and CTLA4 +49A/G (G vs. A).

Table 2. Results from different comparative genetic models in CTLA4 +49A/G (rs231775).

				Statistical method				Test of heterogeneity			Publication bias
Genetic t model	Overall or subgroup	Numbers of studies	Numbers of participants	OR (95% CI)	Z value	p Value	Model	Chi^2	pHet	I^2 (%)	Begg’s	Egger’s
GG + AG versus AA	All	9	1805	1.19 (0.92, 1.55)	1.31	0.19	Fixed	9.80	0.28	18	0.602	0.670
	European	6	1243	1.28 (0.96, 1.71)	1.68	0.09	Fixed	4.41	0.49	0	–	–
	Asian	2	492	1.20 (0.58, 2.48)	0.49	0.56	Fixed	0.34	0.56	0	–	–
	African	1	70	0.19 (0.04, 0.97)	2.00	0.05	Fixed	–	–	–	–	–
GG versus AG + AA	All	9	1805	1.35 (1.05, 1.73)	2.36	0.02	Fixed	5.64	0.69	0	0.009	0.021
	European	6	1243	1.26 (0.92, 1.74)	1.43	0.15	Fixed	0.87	0.97	0	–	–
	Asian	2	492	1.79 (1.15, 2.78)	2.60	0.009	Fixed	0.59	0.44	0	–	–
	African	1	70	0.64 (0.25, 1.64)	0.93	0.35	Fixed	–	–	–	–	–
GG versus AA	All	9	982	1.31(0.94, 1.82)	1.58	0.11	Fixed	7.59	0.47	0	0.048	0.081
	European	6	657	1.41 (0.96, 2.08)	1.74	0.08	Fixed	1.49	0.91	0	–	–
	Asian	2	280	1.58 (0.75, 3.35)	1.20	0.23	Fixed	0.61	0.44	0	–	–
	African	1	45	0.18 (0.03, 1.00)	1.58	0.11	Fixed	–	–	–	–	–
AG versus AA	All	9	1261	1.08 (0.82, 1.43)	0.55	0.59	Fixed	8.43	0.39	5	0.754	0.473
	European	6	962	1.19 (0.88, 1.62)	1.13	0.26	Fixed	3.81	0.58	0	–	–
	Asian	2	265	0.85 (0.39, 1.86)	0.40	0.69	Fixed	0.16	0.69	0	–	–
	African	1	34	0.19 (0.03, 1.11)	0.55	0.59	Fixed	–	–	–	–	–
G versus A	All	9	3610	1.21(1.03, 1.42)	2.30	0.02	Fixed	9.84	0.28	19	0.118	0.204
	European	6	2486	1.20 (1.00, 1.45)	1.93	0.05	Fixed	2.61	0.76	0	–	–
	Asian	2	984	1.47 (1.04, 2.07)	2.18	0.03	Fixed	0.61	0.44	0	–	–
	African	1	140	0.51 (0.25, 1.05)	1.82	0.07	Fixed	–	–	–	–	–

Notes: OR, odds ratio; CI, confidence interval; Z, test for overall effect; I², index of heterogeneity; p_Het, p value for heterogeneity; G, guanine; A, adenine; C, cytosine; T, thymine; Fixed, fixed effect model; Random, random effect model.

Figure 7. A metacum analysis in CTLA4 +49 GG versus GA+AA.

Figure 8. A metacum analysis in CTLA4 +49 G versus A.