Colomina Jose M, Cavallé-Busquets Pere, Fernàndez-Roig Sílvia, Solé-Navais Pol, Fernandez-Ballart Joan D, Ballesteros Mónica, Ueland Per M, Meyer Klaus, Murphy Michelle M
Area of Preventive Medicine and Public Health, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, IISPV, C/Sant Llorenç 21, Reus 43201, Spain.
Ciberobn Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto Carlos III, Madrid 28029, Spain.
Nutrients. 2016 Oct 9;8(10):621. doi: 10.3390/nu8100621.
The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW ( < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW ( < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) ( for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], ( < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], < 0.05 to 0.20 [0.04], < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from -0.11 [0.06], = 0.055 to -0.23 [0.06], < 0.001).
During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele.
孕期中，甜菜碱同型半胱氨酸甲基转移酶（BHMT）基因c.716G>A（G：鸟苷；A：腺苷）单核苷酸多态性（SNP）对BHMT途径的影响尚不清楚。我们推测该SNP会损害甜菜碱向二甲基甘氨酸的转化，且叶酸状态会改变其影响。我们研究了来自雷乌斯塔拉戈纳出生队列的612名女性，从妊娠≤12周（GW）开始直至整个孕期。变异的BHMT c.716A等位基因频率为30.8%（95%置信区间（CI）：28.3，33.5）。在血浆叶酸水平正常偏高（>13.4 nmol/L）的参与者中，在≤12 GW时，GA基因型（2.35 [2.23，2.47]）的最小二乘几何平均[95% CI]血浆二甲基甘氨酸（pDMG，µmol/L）低于GG基因型（2.58 [2.46，2.70]）（<0.05）；在15 GW时，GA（2.08 [1.97，2.19]）和AA（1.94 [1.75，2.16]）基因型的pDMG低于GG（2.29 [2.18，2.40]）基因型（<0.05）。在可能存在叶酸缺乏（≤13.4 nmol/L）的参与者中，未观察到基因型之间pDMG的差异（≤12 GW时交互作用的P值为0.023，15 GW时为0.038）。在34 GW时，AA基因型参与者的pDMG低于GG基因型（2.01 [1.79，2.25] 对 2.44 [2.16，2.76]），在分娩时也是如此（2.51 [2.39，2.64] 对 3.00 [2.84，3.18]）（<0.01）。在多元线性回归分析中，与正常偏高叶酸状态相比，可能的缺乏与较高的pDMG相关（β系数[标准误]范围从0.07 [0.04]，<0.05到0.20 [0.04]，<0.001，在孕早期和孕中晚期模型中），与GG基因型相比，AA基因型与较低的pDMG相关（β系数[标准误]范围从 -0.11 [0.06]，=0.055到 -0.23 [0.06]，<0.001）。
孕期中，BHMT途径受叶酸状态和变异的BHMT c.716A等位基因影响。
