Table 5.

Studies that have investigated the involvement of MTHFD1 rs2236225, MTRR rs1801394, SLC19A1 rs1051266, GNMT rs10948059, DNMT3B rs2424913, and FPGS rs1544105 in CHD development. GNMT, DNMT3B, and FPGS have not been studied in association with CHDs. MTHFD1, trifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase/synthase; MTRR, methyl-tetrahydrofolate-homocysteine methyltransferase reductase; GNMT, glycine N-methyltransferase; DNMT3B, DNA (cytosine-5-)-methyltransferase 3 beta; FPGS, folypolyglutamyl synthase; SLC19A1, solute carrier family 19 member 1; CHDs, congenital heart defects.

Study	Study Design	Population	Number Cases/Controls	Gene	Single Nucleotide Polymorphism	CHD Risk Genotype or Allele
Christensen KE et al., 2008 [11]	Mother-child pair, case-control	N. European	Children: 158/110Mothers: 199/105	MTHFD1	rs2236225	AA (increased risk)
Zeng W et al., 2011 [35]	Case-control	Chinese Han	599/672	MTRR	rs1801394	GG (increased risk)
Cai B et al., 2014 [12]	Meta-analysis	Mixed	914/964441 families	MTRR	rs1801394	G allele (increased risk)
Pei L et al., 2006 [13]	Case-control, family based	Chinese	Families: 67/100	SLC19A1	rs1051266	G allele (increased risk)
Gong D et al., 2012. [24]	Case-control	Chinese Han	244/136	MTHFD1	rs2236225	No association
				SLC19A1	rs1051266	A allele (increased risk)
Christensen KE et al., 2013 [36]	Mother-child pair, case-control	N. European	Children: 156/69	MTRR	rs1801394	G allele (decreased risk)
			Mothers: 181/65	SLC19A1	rs1051266	No association
Wang B et al., 2013 [15]	Case-control	Chinese	160/188	MTHFD1	rs2236225	No association
				MTRR	rs1801394	No association
				SLC19A1	rs1051266	No association
Mitchell LE et al., 2010 [16]	Family based	Mixed	386 case-family triads	MTRR	rs1801394	No association
Goldmuntz E et al., 2008 [37]	Family based	Mixed	727 case-family triads	MTRR	rs1801394	No association
Huang J et al., 2014 [25]	Case-control	Chinese	173/2017	MTHFD1	rs2236225	No association (GG more prevalent in cases than controls)
Shaw GM et al., 2009 [26]	Case-control	Mixed	214/359	MTHFD1	rs2236225	No association
Guo KN et al., 2017 [38]	Parents of cases and controls	Chinese Han	99/114	MTRR	rs1801394	G allele (increased risk)
Yu D et al., 2014 [39]	Meta-analysis Asian	Caucasian	3.592/3.638	MTRR	rs1801394	G allele (increased risk)
Elizabeth KE et al., 2017 [40]	Mother-child pair, case-control	Indian	Pairs: 32/32	MTRR	rs1801394	G allele (increased risk)
Hassan FM et al., 2017 [41]	Case-control	Egyptian	100/100	MTRR	rs1801394	G allele (increased risk)
Present study	Case-control and family based	Caucasian	Case-control: 199/199Family triads: 44	MTHFD1	rs2236225	GG (increased risk)
				MTRR	rs1801394	AA (increased risk)
				SLC19A1	rs1051266	A allele (increased risk)
				GNMT	rs10948059	TT (increased risk)
				DNMT3B	rs2424913	CC (increased risk)
				FPGS	rs1544105	TT (increased risk)