Background
Methods
Patients and controls
Type of conotruncal heart defect | No. (%) |
---|---|
Tetralogy of Fallot | 90 (46.6) |
Pulmonary atresia with ventricular septal defect | 31 (16.1) |
Double outlet of right ventricle | 35 (18.1) |
Transposition of the great arteries | 10 (5.2) |
Persistent truncus arteriosus | 14 (7.3) |
Interrupted aortic arch | 13 (6.7) |
Total | 193 |
Polymorphism detection
Statistical analysis
Results
Allele frequencies
Genotyped SNPs | Controls (n = 234) | CTD (N = 193) | p-Value for HWE test |
---|---|---|---|
% (No.) | % (No.) | ||
MTHFR C677T (rs1801133) | |||
C | 61.1(286) | 51.3(198) | 0.004* |
T | 38.9(182) | 48.7(188) | |
MTHFR A1298C (rs1801131) | |||
A | 61.3(287) | 47.9(185) | < 0.001* |
C | 38.7(181) | 52.1(201) | |
SLC19A1 G80A (rs1051266) | |||
G | 59.8(280) | 53.1(205) | 0.0485* |
A | 40.2(188) | 46.9(181) | |
MTR A2576G (rs1805087) | |||
A | 41.5(194) | 61.9(239) | 0.7862 |
G | 58.5(174) | 38.1(147) | |
MTRR A66G (rs1801394) | |||
A | 56.8(266) | 60.6(234) | 0.2639 |
G | 43.2(202) | 39.4(152) |
Association of folate-related SNPs with risk of CTDs
Genotype | Controls (n = 234) | CTD (N = 193) | p-Value | |
---|---|---|---|---|
No. (%) | No. (%) | OR (95% CI) | ||
MTHFR C677T | ||||
CC | 83(35.47) | 65(33.68) | 1.00 | |
CT | 120(51.28) | 68(35.23) | 0.72(0.47–1.11) | 0.1493 |
TT | 31(13.25) | 60(31.09) | 2.47(1.42–4.32) | 0.0009* |
CT + TT | 151(64.53) | 128(66.32) | 1.08(0.73–1.62) | 0.6987 |
MTHFR A1298C | ||||
AA | 110(47.01) | 57(29.53) | 1.00 | |
AC | 67(28.63) | 71(36.79) | 2.05(1.28–3.21) | 0.0023* |
CC | 57(24.36) | 65(33.68) | 2.20(1.38–3.58) | 0.0011* |
AC + CC | 124(52.99) | 136(70.47) | 2.12(1.40–3.19) | 0.0002* |
SLC19A1 G80A | ||||
GG | 102(43.59) | 68(35.23) | 1.00 | |
AG | 82(35.04) | 69(35.75) | 1.26(0.82–1.96) | 0.3031 |
AA | 50(21.37) | 56(29.02) | 1.68(1.02–2.70) | 0.0371* |
AG + AA | 132(56.41) | 125(64.77) | 1.42(0.96–2.09) | 0.0791 |
MTR A2756G | ||||
AA | 87(37.18) | 66(34.20) | 1.00 | |
AG | 120(51.28) | 107(55.44) | 1.18(0.77–1.76) | 0.4426 |
GG | 27(11.54) | 20(10.36) | 0.98(0.51–1.92) | 0.9436 |
AG + GG | 147(62.82) | 127(65.80) | 1.14(0.77–1.70) | 0.5224 |
MTRR A66G | ||||
AA | 75(32.05) | 71(36.79) | 1.00 | |
AG | 116(49.57) | 92(47.67) | 0.84(0.55–1.28) | 0.4136 |
GG | 43(18.38) | 30(15.54) | 0.74(0.42–1.32) | 0.2917 |
AG + GG | 159(67.95) | 122(63.21) | 0.81(0.54–1.21) | 0.3045 |
Association of folate-related SNPs with risk of TOF, PA/VSD, DORV, TGA, PTA, and IAA
Genotype | Controls (n = 234) | TOF (n = 90) | p-Value | PA/VSD (n = 31) | p-Value | DORV (n = 35) | p-Value | TGA (n = 10) | p-Value | PTA (n = 14) | p-Value | IAA (n = 13) | p-Value | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No. (%) | No. (%) | OR (95% CI) | No. (%) | OR (95% CI) | No. (%) | OR (95% CI) | No. (%) | OR (95% CI) | No. (%) | OR (95% CI) | No. (%) | OR (95% CI) | |||||||
MTHFR C677T | |||||||||||||||||||
CC | 83(35.47) | 31(34.44) | 1.00 | 13(41.94) | 1.00 | 9(25.71) | 1.00 | 2(20.00) | 1.00 | 6(42.86) | 1.00 | 4(30.77) | 1.00 | ||||||
CT | 120(51.28) | 32(35.56) | 0.71(0.41–1.24) | 0.2347 | 11(35.48) | 0.59(0.26–1.39) | 0.2130 | 13(37.14) | 0.99(0.40–2.39) | 0.9984 | 5(50.00) | 1.73(0.36–8.84) | 0.5140 | 4(28.57) | 0.46(0.14–1.80) | 0.2315 | 3(23.08) | 0.52(0.13–1.98) | 0.3906 |
TT | 31(13.25) | 27(30.00) | 2.33(1.18–4.39) | 0.0111* | 7(22.58) | 1.44(0.56–3.90) | 0.4749 | 13(37.14) | 3.87(1.55–9.32) | 0.0034* | 3(30.00) | 4.02(0.78–23.14) | 0.1120 | 4(28.57) | 1.79(0.54–6.38) | 0.3883 | 6(46.15) | 4.02(1.09–13.12) | 0.0297* |
CT + TT | 151(64.53) | 59(65.56) | 1.05(0.64–1.72) | 0.8625 | 18(58.06) | 0.76(0.36–1.59) | 0.4816 | 26(74.29) | 1.59(0.70–3.60) | 0.2565 | 8(80.00) | 2.20(0.52–10.46) | 0.3147 | 8(57.14) | 0.73(0.24–2.21) | 0.5757 | 9(69.23) | 1.24(0.38–3.72) | 0.7298 |
MTHFR A1298C | |||||||||||||||||||
AA | 110(47.01) | 27(30.00) | 1.00 | 11(35.48) | 1.00 | 10(28.57) | 1.00 | 4(40.00) | 1.00 | 3(21.43) | 1.00 | 2(15.38) | 1.00 | ||||||
AC | 67(28.63) | 33(36.67) | 2.01(1.11–3.70) | 0.0201* | 13(41.94) | 1.94(0.80–4.39) | 0.1255 | 12(34.29) | 1.97(0.85–4.87) | 0.1313 | 2(20.00) | 0.82(0.15–3.61) | 0.8222 | 7(50.00) | 3.83(1.00–13.90) | 0.0431* | 4(30.77) | 3.28(0.74–17.52) | 0.1543 |
CC | 57(24.36) | 30(33.33) | 2.14(1.14–3.88) | 0.0133* | 7(22.58) | 1.23(0.47–3.39) | 0.6869 | 13(37.14) | 2.51(1.00–6.13) | 0.0369* | 4(40.00) | 1.93(0.54–6.80) | 0.3575 | 4(28.57) | 2.57(0.67–10.43) | 0.2113 | 7(53.85) | 6.75(1.41–32.67) | 0.008* |
AC + CC | 124(52.99) | 63(70.00) | 2.07(1.22–3.50) | 0.0055* | 20(64.52) | 1.61(0.76–3.63) | 0.2261 | 25(71.43) | 2.22(1.02–4.61) | 0.0407* | 6(60.00) | 1.33(0.35–4.26) | 0.6635 | 11(78.57) | 3.25(0.97–11.09) | 0.0619 | 11(84.62) | 4.88(1.15–22.36) | 0.0258* |
SLC19A1 G80A | |||||||||||||||||||
GG | 102(43.59) | 29(32.22) | 1.00 | 13(41.94) | 1.00 | 15(42.86) | 1.00 | 3(30.00) | 1.00 | 3(21.43) | 1.00 | 5(38.46) | 1.00 | ||||||
AG | 82(35.04) | 35(38.89) | 1.62(0.93–2.87) | 0.0987 | 12(38.71) | 1.24(0.51–2.90) | 0.6163 | 10(28.57) | 0.89(0.38–2.06) | 0.7983 | 1(10.00) | 0.45(0.03–3.06) | 0.4786 | 5(35.71) | 2.24(0.57–8.62) | 0.2691 | 6(46.15) | 1.61(0.45–4.84) | 0.4416 |
AA | 50(21.37) | 26(28.89) | 1.63(0.88–2.99) | 0.1205 | 6(19.35) | 0.84(0.31–2.26) | 0.7387 | 10(28.57) | 1.21(0.51–2.85) | 0.6593 | 6(60.00) | 3.64(0.96–13.59) | 0.0593 | 6(42.86) | 3.64(0.96–13.59) | 0.0593 | 2(15.38) | 0.73(0.14–3.58) | 0.7094 |
AG + AA | 132(56.41) | 61(67.78) | 1.63(0.96–2.70) | 0.0618 | 18(58.06) | 1.07(0.51–2.22) | 0.8614 | 20(57.14) | 1.03(0.50–2.12) | 0.9350 | 7(70.00) | 1.80(0.49–6.53) | 0.3953 | 11(78.57) | 2.83(0.84–9.67) | 0.1031 | 8(61.54) | 1.24(0.38–3.44) | 0.7165 |
MTR A2756G | |||||||||||||||||||
AA | 87(37.18) | 33(36.67) | 1.00 | 13(41.94) | 1.00 | 10(28.57) | 1.00 | 2(20.00) | 1.00 | 3(21.43) | 1.00 | 5(38.46) | 1.00 | ||||||
AG | 120(51.28) | 46(51.11) | 1.01(0.59–1.70) | 0.9686 | 15(48.39) | 0.84(0.39–1.83) | 0.6585 | 21(60.00) | 1.52(0.70–3.29) | 0.3018 | 6(60.00) | 2.18(0.52–10.77) | 0.3373 | 11(78.57) | 2.66(0.78–9.10) | 0.1289 | 8(61.54) | 1.16(0.35–3.24) | 0.8003 |
GG | 27(11.54) | 11(12.22) | 1.07(0.50–2.37) | 0.8623 | 3(9.68) | 0.74(0.21–2.60) | 0.6609 | 4(11.43) | 1.29(0.42–4.40) | 0.6871 | 2(20.00) | 3.22(0.48–21.06) | 0.2295 | 0(0.00) | NA | NA | 0(0.00) | NA | NA |
AG + GG | 147(62.82) | 57(63.33) | 1.02(0.61–1.72) | 0.9318 | 18(58.06) | 0.82(0.39–1.71) | 0.6077 | 25(71.43) | 1.48(0.67–3.10) | 0.3226 | 8(80.00) | 2.37(0.56–11.26) | 0.2691 | 11(78.57) | 2.17(0.64–7.42) | 0.2338 | 8(61.54) | 0.95(0.29–2.64) | 0.9259 |
MTRR A66G | |||||||||||||||||||
AA | 75(32.05) | 36(40.00) | 1.00 | 14(45.16) | 1.00 | 12(34.29) | 1.00 | 3(30.00) | 1.00 | 2(14.29) | 1.00 | 4(30.77) | 1.00 | ||||||
AG | 116(49.57) | 46(51.11) | 0.83(0.48–1.38) | 0.4747 | 16(51.61) | 0.74(0.33–1.54) | 0.4423 | 11(31.43) | 0.59(0.26–1.36) | 0.2338 | 3(30.00) | 0.65(0.15–2.83) | 0.5966 | 9(64.29) | 0.29(0.73–13.68) | 0.1615 | 7(53.85) | 1.13(0.34–3.55) | 0.8478 |
GG | 43(18.38) | 8(8.89) | 0.39(0.17–0.88) | 0.026* | 1(3.23) | 0.12(0.01–0.71) | 0.021* | 12(34.29) | 1.74(0.75–4.03) | 0.2139 | 4(40.00) | 2.33(0.60–9.50) | 0.2719 | 3(21.43) | 2.62(0.51–15.07) | 0.2862 | 2(15.38) | 0.87(0.16–3.88) | 0.8773 |
AG + GG | 159(67.95) | 54(60.00) | 0.71(0.43–1.18) | 0.1769 | 17(54.84) | 0.57(0.27–1.19) | 0.1464 | 23(65.71) | 0.90(0.42–1.91) | 0.7921 | 7(70.00) | 1.10(0.29–4.00) | 0.8917 | 12(85.71) | 2.83(0.69–12.93) | 0.1629 | 11(84.62) | 1.06(0.44–3.81) | 0.9232 |
MTHFR C677T, A1298C, and SLC19A1 G80A combined genotype frequencies and risk of CTDs
Genotype | Controls (n = 234) | CTD (N = 193) | p-Value | |
---|---|---|---|---|
No. (%) | No. (%) | OR (95% CI) | ||
MTHFR C677T and A1298C combinations | ||||
677CC, 1298AA | 32(13.68) | 23(11.92) | 1.00 | |
677CC, 1298 AC + CC | 51(21.79) | 42(21.76) | 1.15(0.60–2.23) | 0.6921 |
1298AA, 677CT + TT | 78(33.33) | 34(17.62) | 0.61(0.32–1.17) | 0.1421 |
Either one variant genotype | 129(55.13) | 76(39.38) | 0.82(0.44–1.49) | 0.5199 |
Both variant genotypes | 73(31.20) | 94(48.70) | 1.79(0.95–3.33) | 0.0623 |
MTHFR C677T and SLC19A1 G80A combinations | ||||
677CC, 80GG | 35(14.96) | 21(10.88) | 1.00 | |
677CC, 80AG + AA | 48(20.51) | 44(22.80) | 1.53(0.76–3.03) | 0.2196 |
80GG, 677CT + TT | 67(28.63) | 47(24.35) | 1.17(0.60–2.23) | 0.6410 |
Either one variant genotype | 115(49.15) | 91(47.15) | 1.32(0.72–2.44) | 0.3706 |
Both variant genotypes | 84(35.90) | 81(41.97) | 1.61(0.85–3.05) | 0.1327 |
MTHFR A1298C and SLC19A1 G80A combinations | ||||
1298AA, 80GG | 46(19.66) | 18(9.33) | 1.00 | |
1298AA, 80AG + AA | 64(27.35) | 39(20.21) | 1.56(0.79–3.14) | 0.1969 |
80GG, 1298 AC + CC | 56(23.93) | 50(25.91) | 2.28(1.18–4.53) | 0.0141* |
Either one variant genotype | 120(51.28) | 89(46.11) | 1.90(1.05–3.40) | 0.0382* |
Both variant genotypes | 68(29.06) | 86(44.56) | 3.23(1.71–6.02) | 0.0002* |
MTHFR C677T, A1298C and SLC19A1 G80A combinations | ||||
677CC, 1298AA, 80GG | 12(5.13) | 10(5.18) | 1.00 | |
677CC, 1298AA, 80AG + AA | 20(8.55) | 11(5.70) | 0.66(0.20–2.09) | 0.4646 |
677CC, 80GG, 1298 AC + CC | 23(9.83) | 11(5.70) | 0.57(0.18–1.77) | 0.3226 |
1298AA, 80GG, 677CT + TT | 34(14.53) | 10(5.18) | 0.35(0.11–1.06) | 0.0582 |
Either one variant genotype | 77(32.91) | 32(16.58) | 0.50(0.20–1.34) | 0.1400 |
677CC, 1298 AC + CC, 80AG + AA | 28(11.97) | 31(16.06) | 1.33(0.48–3.32) | 0.5704 |
677CT + TT, 1298AA, 80AG + AA | 44(18.80) | 26(13.47) | 0.71(0.26–1.78) | 0.4859 |
677CT + TT, 1298 AC + CC, 80GG | 33(14.10) | 39(20.21) | 1.42(0.54–3.52) | 0.4740 |
Either two variant genotypes | 105(44.87) | 96(49.74) | 1.10(0.48–2.67) | 0.8370 |
All variant genotypes | 40(17.09) | 55(28.50) | 1.65(0.66–4.40) | 0.2900 |