. 2014 Dec 4;2014:517504. doi: 10.1155/2014/517504

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 (n)	Test of association		Test of heterogeneity			Tests of publication bias (P value)
Polymorphism	Comparison	Population	Study (n)	OR (95% CI)	P value (Z test)	χ ²	I ²	P 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 (0.97–1.33)^b	0.11	7.01	0%	0.43	0.27	0.20
		Caucasian	3	1.08 (0.84–1.40)^b	0.55	2.69	26%	0.26	—	—
		Brazilian	5	1.17 (0.96–1.42)^b	0.12	4.11	3%	0.39	0.48	0.65
	GG versus AG/AA	All	8	1.18 (0.80–1.76)^b	0.41	3.69	0%	0.81	0.27	0.34
		Caucasian	3	0.80 (0.35–1.82)^b	0.60	0.72	0%	0.70	—	—
		Brazilian	5	1.34 (0.85–2.12)^b	0.21	1.92	0%	0.75	0.23	0.18
	AG versus AA	All	8	1.13 (0.96–1.33)^b	0.15	9.26	24%	0.23	0.06	0.16
		Caucasian	3	1.10 (0.85–1.44)^b	0.46	3.24	38%	0.20	—	—
		Brazilian	5	1.14 (0.93–1.40)^b	0.21	5.99	33%	0.20	0.48	0.58
	GG versus AA	All	8	1.25 (0.84–1.88)^b	0.27	2.97	0%	0.89	0.54	0.43
		Caucasian	3	0.85 (0.37–1.94)^b	0.70	0.61	0%	0.74	—	—
		Brazilian	5	1.42 (0.89–2.27)^b	0.14	1.28	0%	0.86	0.48	0.19
	G versus A	All	8	1.11 (0.97–1.26)^b	0.14	5.33	0%	0.62	0.27	0.29
		Caucasian	3	1.04 (0.83–1.31)^b	0.71	1.82	0%	0.40	—	—
		Brazilian	5	1.14 (0.96–1.34)^b	0.12	3.18	0%	0.53	0.81	0.73

MTRR c.66A>G	GG/AG versus AA	All	13	1.29 (1.09–1.53)^b	0.003	18.68	36%	0.10	0.25	0.08
		All in HWE	11	1.28 (1.00–1.65)^a	0.05	18.42	46%	0.05	0.21	0.06
		Caucasian	6	1.42 (1.08–1.88)^b	0.01	9.39	47%	0.09	0.46	0.31
		Brazilian	6	1.14 (0.91–1.42)^b	0.25	4.87	0%	0.43	0.46	0.89
	GG versus AG/AA	All	13	1.33 (1.03–1.71)^a	0.03	26.11	54%	0.01	0.59	0.27
		All in HWE	11	1.37 (1.00–1.88)^a	0.05	25.82	61%	0.004	0.44	0.34
		Caucasian	6	1.43 (1.13–1.83)^b	0.003	9.44	47%	0.09	0.46	0.64
		Brazilian	6	1.09 (0.86–1.37)^b	0.47	8.35	40%	0.14	0.71	0.44
	AG versus AA	All	13	1.22 (1.01–1.47)^b	0.04	12.47	4%	0.41	0.36	0.17
		All in HWE	11	1.20 (0.99–1.47)^b	0.07	12.11	17%	0.28	0.44	0.13
		Caucasian	6	1.31 (0.98–1.75)^b	0.07	7.89	37%	0.16	0.46	0.36
		Brazilian	6	1.11 (0.86–1.43)^b	0.44	2.98	0%	0.70	0.46	0.60
	GG versus AA	All	13	1.57 (1.07–2.31)^a	0.02	28.81	58%	0.004	0.30	0.07
		All in HWE	11	1.61 (1.02–2.53)^a	0.04	28.72	65%	0.001	0.35	0.07
		Caucasian	6	1.65 (0.95–2.88)^a	0.08	10.87	54%	0.05	>0.99	0.41
		Brazilian	6	1.16 (0.83–1.62)^b	0.37	9.88	49%	0.08	>0.99	0.33
	G versus A	All	13	1.18 (0.99–1.40)^a	0.07	35.50	66%	0.0004	0.20	0.12
		All in HWE	11	1.20 (0.96–1.49)^a	0.10	35.38	72%	0.0001	0.28	0.12
		Caucasian	6	1.26 (0.96–1.66)^a	0.10	13.85	64%	0.02	>0.99	0.84
		Brazilian	6	1.00 (0.88–1.14)^b	0.97	8.26	39%	0.14	0.71	0.64

CβS c.844ins68	Ins +/+ + Ins −/+ versus Ins −/−	All	6	1.03 (0.80–1.31)^b	0.84	2.60	0%	0.76	0.13	0.22
	Ins +/+ + Ins −/+ versus Ins −/−	Brazilian	4	1.10 (0.83–1.45)^b	0.51	1.37	0%	0.71	0.75	0.79
	Ins +/+ versus Ins −/+ + Ins −/−	All	6	1.07 (0.50–2.28)^b	0.86	2.96	0%	0.56	0.75	0.73
	Ins +/+ versus Ins −/+ + Ins −/−	Brazilian	4	1.17 (0.53–2.56)^b	0.70	2.42	0%	0.49	0.75	0.75
	Ins −/+ versus Ins −/−	All	6	1.02 (0.79–1.32)^b	0.87	3.33	0%	0.65	0.27	0.36
	Ins −/+ versus Ins −/−	Brazilian	4	1.09 (0.81–1.45)^b	0.57	2.47	0%	0.48	0.75	0.99
	Ins +/+ versus Ins −/−	All	6	1.10 (0.51–2.34)^b	0.81	2.69	0%	0.61	0.75	0.74
	Ins +/+ versus Ins −/−	Brazilian	4	1.20 (0.54–2.64)^b	0.65	2.10	0%	0.55	0.33	0.76
	Ins + versus Ins −	All	6	1.07 (0.86–1.34)^b	0.54	1.33	0%	0.93	0.71	0.65
	Ins + versus Ins −	Brazilian	4	1.07 (0.83–1.37)^b	0.61	0.51	0%	0.92	0.33	0.21

MTHFD-1 c.1958G>A	AA + GA versus GG	All	5	1.22 (0.96–1.55)^b	0.10	1.86	0%	0.76	0.48	0.38
	AA + GA versus GG	All in HWE	4	1.28 (0.98–1.67)^b	0.07	1.16	0%	0.76	0.33	0.21
	AA versus GA + GG	All	5	0.96 (0.71–1.30)^b	0.79	1.61	0%	0.81	0.08	0.43
	AA versus GA + GG	All in HWE	4	0.96 (0.68–1.37)^b	0.84	1.60	0%	0.66	0.33	0.53
	GA versus GG	All	5	1.26 (0.98–1.62)^b	0.07	2.62	0%	0.62	0.48	0.37
	GA versus GG	All in HWE	4	1.33 (1.01–1.75)^b	0.04	1.86	0%	0.60	0.75	0.27
	AA versus GG	All	5	1.05 (0.74–1.50)^b	0.77	0.66	0%	0.96	0.81	0.81
	AA versus GG	All in HWE	4	1.09 (0.73–1.62)^b	0.67	0.54	0%	0.91	0.75	0.85
	A versus G	All	5	1.08 (0.92–1.27)^b	0.35	1.30	0%	0.86	0.48	0.40
	A versus G	All in HWE	4	1.11 (0.93–1.33)^b	0.26	0.87	0%	0.83	0.75	0.39

TC2 c.776C>G	GG + CG versus CC	All	4	1.27 (0.83–1.93)^a	0.27	8.03	63%	0.05	0.33	0.53
	GG + CG versus CC	All in HWE	2	0.92 (0.64–1.32)^b	0.66	0.38	0%	0.53	—	—
	GG versus CG + CC	All	4	0.94 (0.70–1.27)^b	0.70	5.65	47%	0.13	0.75	0.91
	GG versus CG + CC	All in HWE	2	1.12 (0.40–3.16)^a	0.83	4.32	77%	0.04	—	—
	CG versus CC	All	4	1.34 (0.82–2.19)^a	0.25	9.74	69%	0.02	0.75	0.67
	CG versus CC	All in HWE	2	0.89 (0.61–1.31)^b	0.56	0	0%	0.96	—	—
	GG versus CC	All	4	1.22 (0.87–1.72)^b	0.25	4.61	35%	0.20	0.75	0.57
	GG versus CC	All in HWE	2	1.04 (0.61–1.78)^b	0.88	3.60	72%	0.06	—	—
	G versus C	All	4	1.12 (0.95–1.32)^b	0.19	6.17	51%	0.10	0.08	0.20
	G versus C	All in HWE	2	0.97 (0.75–1.25)^b	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.