Department of paediatrics, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
Department of science and education, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
BMC Pediatr. 2018 Aug 30;18(1):287. doi: 10.1186/s12887-018-1266-9.
Conotruncal heart defects (CTDs) are a subgroup of congenital heart defects that are considered to be the most common type of birth defect worldwide. Genetic disturbances in folate metabolism may increase the risk of CTDs.
We evaluated five single-nucleotide polymorphisms (SNPs) in genes related to folic acid metabolism: methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), solute carrier family 19, member 1 (SLC19A1 G80A), methionine synthase (MTR A2576G), and methionine synthase reductase (MTRR A66G), as risk factors for CTDs including various types of malformation, in a total of 193 mothers with CTD-affected offspring and 234 healthy controls in a Chinese population.
Logistic regression analyses revealed that subjects carrying the TT genotype of MTHFR C677T, the C allele of MTHFR A1298C, and the AA genotype of SLC19A1 G80A had significant 2.47-fold (TT vs. CC, OR [95% CI] = 2.47 [1.42-4.32], p = 0.009), 2.05-2.20-fold (AC vs. AA, 2.05 [1.28-3.21], p = 0.0023; CC vs AA, 2.20 [1.38-3.58], p = 0.0011), and 1.68-fold (AA vs. GG, 1.68 [1.02-2.70], p = 0.0371) increased risk of CTDs, respectively. Subjects carrying both variant genotypes of MTHFR A1298C and SLC19A1 G80A had a higher (3.23 [1.71-6.02], p = 0.0002) increased risk for CTDs. Moreover, the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms were found to be significantly associated with the risk of certain subtypes of CTD.
Our data suggest that maternal folate-related SNPs might be associated with the risk of CTDs in offspring.
圆锥动脉干畸形（CTD）是一组先天性心脏病，被认为是全球最常见的出生缺陷类型。叶酸代谢中的遗传干扰可能会增加 CTD 的风险。
我们评估了与叶酸代谢相关的五个单核苷酸多态性（SNP）：亚甲基四氢叶酸还原酶（MTHFR C677T 和 A1298C）、溶质载体家族 19 成员 1（SLC19A1 G80A）、蛋氨酸合成酶（MTR A2576G）和蛋氨酸合成酶还原酶（MTRR A66G），作为包括各种畸形类型的 CTD 的危险因素，在一个中国人群中，共有 193 名患有 CTD 患儿的母亲和 234 名健康对照者中进行了研究。
Logistic 回归分析显示，携带 MTHFR C677T 的 TT 基因型、MTHFR A1298C 的 C 等位基因和 SLC19A1 G80A 的 AA 基因型的受试者具有显著的 2.47 倍（TT 与 CC，OR [95%CI] = 2.47 [1.42-4.32]，p = 0.009）、2.05-2.20 倍（AC 与 AA，2.05 [1.28-3.21]，p = 0.0023；CC 与 AA，2.20 [1.38-3.58]，p = 0.0011）和 1.68 倍（AA 与 GG，1.68 [1.02-2.70]，p = 0.0371）的 CTD 风险增加。携带 MTHFR A1298C 和 SLC19A1 G80A 两个变异基因型的受试者具有更高的 CTD 风险（3.23 [1.71-6.02]，p = 0.0002）。此外，MTHFR C677T、MTHFR A1298C 和 MTRR A66G 多态性与 CTD 的某些亚型的风险显著相关。
我们的数据表明，母体叶酸相关 SNP 可能与后代 CTD 的风险相关。
