Association between the RAGE gene -374T/A, -429T/C polymorphisms and diabetic nephropathy: a meta-analysis

Figures & data

Table 1. Characteristics of the case–control studies considered in the meta-analysis.

First author	Year	Country	Ethnicity	SNP	Genotyping	DM type	DN selection criteria
Poirier O13	2001	France	Caucasian	-374T/A	Radioactive SSCP	T1DM	Albuminuria
Kim PF14	2003	Finland	Caucasian	-374T/A	Solid-phase minisequencing	T1DM	AER>200 µg/min or >300 mg/24 h
Xu JX15	2004	China	Asian	-429T/C	RFLP	T2DM	AER≥20 µg/min. Patients with end-stage renal disease and renal transplantation were excluded
Xu JX16	2005	China	Asian	-374T/A	RFLP	T2DM	AER≥20 µg/min. Patients with end-stage renal disease and renal transplantation were excluded
Kankova K17	2005	Czech	Caucasian	-374T/A, -429T/C	RFLP	T2DM	AER≥30 mg/24 h
Santos KG18	2005	Brazil	Caucasian, African	-374T/A, -429T/C	RFLP	T2DM	AER≥20 µg/min or 17 mg/L
Lindholm E19	2008	Sweden	Caucasian	-374T/A	Allelic discrimination	T1DM T2DM	AER≥20 µg/min or ≥30 mg/24 h or UACR≥2.0 g/mol in males or ≥2.8 g/mol in females
Prasad P20	2010	India	Asian	-429T/C	RFLP	T2DM	Chronic renal insufficiency, serum creatinine≥3.0 mg/dL

Notes: SNP, single-nucleotide polymorphism; RFLP, restriction fragment length polymorphism; AER, albumin excretion rate; UACR, urinary albumin/creatinine ratio.

Table 2. Distribution of the RAGE gene -374T/A and -429T/C genotypes for cases and controls and the allele frequencies.

				Cases			Controls
First author	Year	Ethnicity	DM type	No.	Genotypes	Alleles	No.	Genotypes	Alleles	p-Value HWE^b
-374T/A polymorphism					TT/TA/AA	T/A (%)		TT/TA/AA	T/A (%)
Poirier O	2001	Caucasian	T1DM	199	87/89/23	66.1/33.9	193	94/81/18	69.7/30.3	0.927
Kim PF	2003	Caucasian	T1DM	321	269^a/48	–	317	280^b/41	–	NA
Xu JX	2005	Asian	T2DM	227	171/51/5	86.6/13.4	126	95/29/2	86.9/13.1	0.900
Kankova K	2005	Caucasian	T2DM	195	82/92/21	65.6/34.4	176	65/90/21	62.5/37.5	0.228
Santos KG	2005	Caucasian	T2DM	258	–	68.0/32.0	195	–	71.0/29.0	NA
Santos KG	2005	African	T2DM	96	60/30/6	78.1/21.9	66	37/21/8	72.0/28.0	0.086
Lindholm E	2008	Caucasian	T2DM	315	183/117/15	76.7/23.3	439	238/165/36	73.0/27.0	0.331
Lindholm E	2008	Caucasian	T1DM	114	39/66/9	63.2/36.8	345	180/142/23	72.8/27.2	0.478
-429T/C polymorphism					TT/TC/CC	T/C (%)		TT/TC/CC	T/C (%)
Xu JX	2004	Asian	T2DM	271	218/51/2	89.9/10.1	127	89/37/1	84.6/15.4	0.173
Kankova K	2005	Caucasian	T2DM	198	125/59/14	78.0/22.0	179	129/46/4	84.9/15.1	0.966
Santos KG	2005	Caucasian	T2DM	258	–	87.0/13.0	195	–	89.0/11.0	NA
Santos KG	2005	African	T2DM	96	71/23/2	85.9/14.1	66	52/12/2	87.9/12.1	0.234
Prasad P	2010	Asian	T2DM	196	159/27/10	88.0/12.0	225	173/50/2	88.0/12.0	0.434

Notes: ^aData concerned (TT+TA); ^bp value for Hardy–Weinberg equilibrium testing for controls; NA, not available.

Figure 1. Random effects odds ratio estimates with the corresponding 95% confidence interval for the allele contrast A versus T of RAGE gene -374T/A polymorphism.

Table 3. Summary of the odds ratio (OR) for genetic contrasts of the association of -374T/A and -429T/C polymorphisms in DN.

Genetic contrasts	Overall and subgroup (studies)	Fixed-effects [FE OR (95% CI)]	Random effects [RE OR (95% CI)]	p-Value Q-test^a	p-Value Z-test^b
-374T/A polymorphism
A versus T	All (7)	1.02 (0.91–1.15)	1.03 (0.85–1.25)	0.03	0.75
	Caucasian (5)	1.05 (0.92–1.19)	1.08 (0.86–1.35)	0.01	0.52
	T2DM (5)	0.92 (0.80–1.06)	0.92 (0.79–1.07)	0.35	0.27
AA versus TT+TA	All (7)	0.96 (0.74–1.23)	0.96 (0.73–1.26)	0.37	0.75
	Caucasian (5)	0.98 (0.75–1.28)	0.99 (0.73–1.33)	0.31	0.93
	T2DM (4)	0.69 (0.47–1.03)	0.69 (0.47–1.04)	0.54	0.08
AA+TA versus TT	All (6)	1.04 (0.88–1.23)	1.06 (0.79–1.43)	0.01	0.70
	Caucasian (4)	1.08 (0.90–1.29)	1.14 (0.76–1.70)	0.004	0.54
	T2DM (4)	0.86 (0.70–1.05)	0.86 (0.70–1.05)	0.90	0.14
-429T/C polymorphism
C versus T	All (5)	1.10 (0.91–1.34)	1.07 (0.78–1.48)	0.03	0.66
CC versus TT+TC	All (4)	2.83 (1.33–6.00)	2.50 (1.00–6.24)	0.29	0.05
CC+TC versus TT	All (4)	0.95 (0.74–1.22)	0.95 (0.59–1.52)	0.02	0.83

Notes: ^ap-Value of heterogeneity test (Q-test); ^bp value for significance (Z-test) under random effects model; HWE, Hardy–Weinberg equilibrium.

Figure 2. Random effects odds ratio estimates with the corresponding 95% confidence interval for the allele contrast C versus T of RAGE gene -429T/C polymorphism.

Figure 3. Fixed-effects odds ratio estimates with the corresponding 95% confidence interval for the recessive model (CC vs. TT+TC) of RAGE gene -429T/C polymorphism.

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