Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis

Table 2

Pooled estimates and stratified analysis for the associations between MTR c.2756A>G (rs1805087), MTRR c.66A>G (rs1801394), TC2 c.776C>G (rs1801198), CBS c.844ins68, and MTHFD1 c.1958G>A (rs2236225) polymorphisms and maternal risk for Down syndrome.

Polymorphism	Comparison	Population	Study ()	Test of association		Test of heterogeneity			Tests of publication bias ( value)
				OR (95% CI)	value ( test)			value	Rank test; (Begg and Mazumdar [46])	Linear regression (Egger et al. [47])
MTR c.2756A>G	GG/AG versus AA	All	8	1.14	0.11	7.01	0%	0.43	0.27	0.20
		Caucasian	3	1.08	0.55	2.69	26%	0.26	—	—
		Brazilian	5	1.17	0.12	4.11	3%	0.39	0.48	0.65
	GG versus AG/AA	All	8	1.18	0.41	3.69	0%	0.81	0.27	0.34
		Caucasian	3	0.80	0.60	0.72	0%	0.70	—	—
		Brazilian	5	1.34	0.21	1.92	0%	0.75	0.23	0.18
	AG versus AA	All	8	1.13	0.15	9.26	24%	0.23	0.06	0.16
		Caucasian	3	1.10	0.46	3.24	38%	0.20	—	—
		Brazilian	5	1.14	0.21	5.99	33%	0.20	0.48	0.58
	GG versus AA	All	8	1.25	0.27	2.97	0%	0.89	0.54	0.43
		Caucasian	3	0.85	0.70	0.61	0%	0.74	—	—
		Brazilian	5	1.42	0.14	1.28	0%	0.86	0.48	0.19
	G versus A	All	8	1.11	0.14	5.33	0%	0.62	0.27	0.29
		Caucasian	3	1.04	0.71	1.82	0%	0.40	—	—
		Brazilian	5	1.14	0.12	3.18	0%	0.53	0.81	0.73
MTRR c.66A>G	GG/AG versus AA	All	13	1.29	0.003	18.68	36%	0.10	0.25	0.08
		All in HWE	11	1.28	0.05	18.42	46%	0.05	0.21	0.06
		Caucasian	6	1.42	0.01	9.39	47%	0.09	0.46	0.31
		Brazilian	6	1.14	0.25	4.87	0%	0.43	0.46	0.89
	GG versus AG/AA	All	13	1.33	0.03	26.11	54%	0.01	0.59	0.27
		All in HWE	11	1.37	0.05	25.82	61%	0.004	0.44	0.34
		Caucasian	6	1.43	0.003	9.44	47%	0.09	0.46	0.64
		Brazilian	6	1.09	0.47	8.35	40%	0.14	0.71	0.44
	AG versus AA	All	13	1.22	0.04	12.47	4%	0.41	0.36	0.17
		All in HWE	11	1.20	0.07	12.11	17%	0.28	0.44	0.13
		Caucasian	6	1.31	0.07	7.89	37%	0.16	0.46	0.36
		Brazilian	6	1.11	0.44	2.98	0%	0.70	0.46	0.60
	GG versus AA	All	13	1.57	0.02	28.81	58%	0.004	0.30	0.07
		All in HWE	11	1.61	0.04	28.72	65%	0.001	0.35	0.07
		Caucasian	6	1.65	0.08	10.87	54%	0.05	>0.99	0.41
		Brazilian	6	1.16	0.37	9.88	49%	0.08	>0.99	0.33
	G versus A	All	13	1.18	0.07	35.50	66%	0.0004	0.20	0.12
		All in HWE	11	1.20	0.10	35.38	72%	0.0001	0.28	0.12
		Caucasian	6	1.26	0.10	13.85	64%	0.02	>0.99	0.84
		Brazilian	6	1.00	0.97	8.26	39%	0.14	0.71	0.64
CβS c.844ins68	Ins +/+ + Ins −/+ versus Ins −/−	All	6	1.03	0.84	2.60	0%	0.76	0.13	0.22
		Brazilian	4	1.10	0.51	1.37	0%	0.71	0.75	0.79
	Ins +/+ versus Ins −/+ + Ins −/−	All	6	1.07	0.86	2.96	0%	0.56	0.75	0.73
		Brazilian	4	1.17	0.70	2.42	0%	0.49	0.75	0.75
	Ins −/+ versus Ins −/−	All	6	1.02	0.87	3.33	0%	0.65	0.27	0.36
		Brazilian	4	1.09	0.57	2.47	0%	0.48	0.75	0.99
	Ins +/+ versus Ins −/−	All	6	1.10	0.81	2.69	0%	0.61	0.75	0.74
		Brazilian	4	1.20	0.65	2.10	0%	0.55	0.33	0.76
	Ins + versus Ins −	All	6	1.07	0.54	1.33	0%	0.93	0.71	0.65
		Brazilian	4	1.07	0.61	0.51	0%	0.92	0.33	0.21
MTHFD-1 c.1958G>A	AA + GA versus GG	All	5	1.22	0.10	1.86	0%	0.76	0.48	0.38
		All in HWE	4	1.28	0.07	1.16	0%	0.76	0.33	0.21
	AA versus GA + GG	All	5	0.96	0.79	1.61	0%	0.81	0.08	0.43
		All in HWE	4	0.96	0.84	1.60	0%	0.66	0.33	0.53
	GA versus GG	All	5	1.26	0.07	2.62	0%	0.62	0.48	0.37
		All in HWE	4	1.33	0.04	1.86	0%	0.60	0.75	0.27
	AA versus GG	All	5	1.05	0.77	0.66	0%	0.96	0.81	0.81
		All in HWE	4	1.09	0.67	0.54	0%	0.91	0.75	0.85
	A versus G	All	5	1.08	0.35	1.30	0%	0.86	0.48	0.40
		All in HWE	4	1.11	0.26	0.87	0%	0.83	0.75	0.39
TC2 c.776C>G	GG + CG versus CC	All	4	1.27	0.27	8.03	63%	0.05	0.33	0.53
		All in HWE	2	0.92	0.66	0.38	0%	0.53	—	—
	GG versus CG + CC	All	4	0.94	0.70	5.65	47%	0.13	0.75	0.91
		All in HWE	2	1.12	0.83	4.32	77%	0.04	—	—
	CG versus CC	All	4	1.34	0.25	9.74	69%	0.02	0.75	0.67
		All in HWE	2	0.89	0.56	0	0%	0.96	—	—
	GG versus CC	All	4	1.22	0.25	4.61	35%	0.20	0.75	0.57
		All in HWE	2	1.04	0.88	3.60	72%	0.06	—	—
	G versus C	All	4	1.12	0.19	6.17	51%	0.10	0.08	0.20
		All in HWE	2	0.97	0.79	2.63	62%	0.10	—	—

OR: odds ratio; CI: confidence interval.
Bold values indicate significant associations.
^aRandom-effect model.
^bFixed-effect model.
—: insufficient strata.