Department of Applied Health Science, Indiana University Bloomington School of Public Health, Bloomington, IN, USA; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Laney Graduate School, Emory University, USA.
Clin Nutr. 2021 Oct;40(10):5339-5345. doi: 10.1016/j.clnu.2021.08.026. Epub 2021 Sep 11.
Variability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment.
To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years.
We conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA).
Maternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions <0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes).
Maternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions.
FADS2 基因的变异会影响 Delta-6 去饱和酶的编码，并调节必需的 n-3 和 n-6 脂肪酸转化为长链多不饱和脂肪酸，这可能会改变产前补充 n-3 二十二碳六烯酸（DHA）对神经发育的影响。
评估母体 FADS2 单核苷酸多态性（SNP）是否会改变产前 DHA 对 5 岁后代发育的影响。
我们对产前补充藻油 DHA 的 POSGRAD 随机对照试验（NCT00646360）进行了事后交互分析，该试验最初将 1094 名孕妇随机分为两组，从妊娠第 18-22 周到分娩，每天分别补充 400mg 藻油 DHA 或安慰剂。在这项分析中，我们纳入了在 5 岁时具有母体基因型和神经发育信息的后代（DHA = 316；对照组 = 306），并使用广义线性模型来评估 FADS2 SNPrs174602 或 rs174575 与产前 DHA 对 5 岁时使用 McCarthy 儿童能力量表（MSCA）测量的神经发育的交互作用。
两组间的母婴特征相似。基线时，母亲的平均（±标准差）年龄为 26 ± 5 岁，受教育程度为 12 ± 4 年。46%的孩子为女性。SNP rs174602 和 rs174575 的母体次要等位基因频率分别为 0.37 和 0.33。SNP rs174602 与干预组之间存在显著差异（交互作用的 p 值 <0.05），干预组中 TT（纯合子）的孩子在定量（DHA：平均 ± SEM = 22.6 ± 0.9 与对照组 = 19.1 ± 0.9，差异（Δ）= 3.45；p = 0.01）和记忆（DHA = 27.9 ± 1.1 与对照组 = 23.7 ± 1.1，Δ = 4.26；p = 0.02）量表上的 MSCA 评分更高。
母体 FADS2 SNP rs174602 改变了产前 DHA 对 5 岁时认知发育的影响。目标人群遗传构成的差异可能是产前 DHA 补充干预的一个重要考虑因素。
