Table 2. Overall and stratified meta-analyses of the association between methylenetetrahydrofolate reductase polymorphism 677C→T and risk of type 2 diabetes mellitus.

Genotype comparison	OR [95% CI]	Z (P value)	Heterogeneity of study design			Analysis model
			χ2	df (P value)	I2
All studies (4855 cases, 5242 controls)
C-allele vs. T-allele	0.91 [0.82, 1.00]	1.97 (0.05)	76.62	38 (<0.001)	50%	Random
CC vs. CT+TT	0.88 [0.75, 1.03]	1.56 (0.12)	95.21	38 (<0.001)	60%	Random
CC vs. TT	0.82 [0.71, 0.95]	2.62 (0.009)	35.40	37 (0.54)	0%	Fixed
TT vs. CC+CT	1.15 [1.03, 1.29]	2.57 (0.01)	26.07	37 (0.91)	0%	Fixed
Subgroups by ethnicity
Asian (3438 cases, 3455 controls)
C-allele vs. T-allele	0.86 [0.76, 0.96]	2.62 (0.009)	45.38	25 (0.008)	45%	Random
CC vs. CT+TT	0.81 [0.66, 0.98]	2.14 (0.03)	59.41	25 (<0.001)	58%	Random
CC vs. TT	0.82 [0.68, 0.99]	2.11 (0.04)	24.34	24 (0.44)	1%	Fixed
TT vs. CC+CT	1.12 [0.99, 1.27]	1.76 (0.08)	19.40	24 (0.73)	0%	Fixed
Caucasian (713 cases, 969 controls)
C-allele vs. T-allele	1.06 [0.91, 1.22]	0.73 (0.47)	4.19	8 (0.84)	0%	Fixed
CC vs. CT+TT	1.22 [0.99, 1.49]	1.91 (0.06)	3.63	8 (0.89)	0%	Fixed
CC vs. TT	0.92 [0.67, 1.27]	0.51 (0.61)	2.25	8 (0.97)	0%	Fixed
TT vs. CC+CT	1.23 [0.91, 1.65]	1.35 (0.18)	2.06	8 (0.98)	0%	Fixed
African (704 cases, 818 controls)
C-allele vs. T-allele	0.75 [0.46, 1.24]	1.12 (0.26)	23.04	3 (<0.001)	87%	Random
CC vs. CT+TT	0.75 [0.39, 1.43]	0.88 (0.38)	23.67	3 (<0.001)	87%	Random
CC vs. TT	0.70 [0.37, 1.31]	1.13 (0.26)	8.05	3 (0.05)	63%	Random
TT vs. CC+CT	1.32 [0.95, 1.83]	1.65 (0.10)	3.59	3 (0.31)	16%	Fixed
Subgroups by DM-related complications
T2DM with serious complications (3062 cases, 3248 controls)
C-allele vs. T-allele	0.91 [0.79, 1.04]	1.37 (0.17)	32.40	13 (0.002)	60%	Random
CC vs. CT+TT	0.96 [0.77, 1.20]	0.38 (0.71)	38.46	13 (<0.001)	66%	Random
CC vs. TT	0.83 [0.69, 1.00]	1.99 (0.05)	20.32	13 (0.09)	36%	Fixed
TT vs. CC+CT	1.17 [1.02, 1.33]	2.32 (0.02)	12.21	13 (0.51)	0%	Fixed
T2DM without serious complications (1793 cases, 1994 controls)
C-allele vs. T-allele	0.90 [0.78, 1.04]	1.43 (0.15)	44.11	24 (0.007)	46%	Random
CC vs. CT+TT	0.83 [0.66, 1.03]	1.68 (0.09)	55.21	24 (<0.001)	57%	Random
CC vs. TT	0.82 [0.65, 1.03]	1.71 (0.09)	15.09	23 (0.89)	0%	Fixed
TT vs. CC+CT	1.13 [0.92, 1.39]	1.13 (0.26)	13.78	23 (0.93)	0%	Fixed
Subgroups by HWE
Alleles in control group in HWE (4281 cases, 4516 controls)
C-allele vs. T-allele	0.91 [0.82, 1.01]	1.75 (0.08)	64.89	34 (0.001)	48%	Random
CC vs. CT+TT	0.89 [0.75, 1.05]	1.36 (0.17)	83.85	34 (<0.001)	59%	Random
CC vs. TT	0.83 [0.70, 0.97]	2.33 (0.02)	28.57	33 (0.69)	0%	Fixed
TT vs. CC+CT	1.16 [1.04, 1.31]	2.53 (0.01)	21.44	33 (0.94)	0%	Fixed
Alleles in control group not in HWE (574 cases, 726 controls)
C-allele vs. T-allele	0.88 [0.63, 1.24]	0.74 (0.46)	10.80	3 (0.01)	72%	Random
CC vs. CT+TT	0.83 [0.54, 1.26]	0.88 (0.38)	7.81	3 (0.05)	62%	Random
CC vs. TT	0.88 [0.51, 1.51]	0.46 (0.64)	6.80	3 (0.08)	56%	Random
TT vs. CC+CT	1.09 [0.81, 1.48]	0.57 (0.57)	4.52	3 (0.21)	34%	Fixed