Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial.
Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial.
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DOI：
10.1016/j.clnu.2021.08.026
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发表时间：
2021-10
影响因子：
6.3
通讯作者：
Ramakrishnan, Usha
中科院分区：
文献类型：
--
作者：
Casanova, Ines Gonzalez;Schoen, Meriah;Tandon, Sonia;Stein, Aryeh D.;Villarreal, Albino Barraza;DiGirolamo, Ann M.;Demmelmair, Hans;Silva, Ivonne Ramirez;Feregrino, Raquel Garcia;Rzehak, Peter;Stevenson, India;Standl, Marie;Schnaas, Lourdes;Romieu, Isabelle;Koletzko, Berthold;Ramakrishnan, Usha
关键词：
FADS2基因编码Delta-6去饱和酶，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，该基因的变异性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。为了评估母亲FADS2单核苷酸多态(SNPs)是否改变了产前DHA对5岁时后代发育的影响。我们进行了POSGRAD随机对照试验(NCT00646360)产前补充藻类DHA的随机交互作用分析，其中1,094名孕妇最初随机接受从妊娠18-22周到分娩期间每天400毫克的预制藻类DHA或安慰剂。在这项分析中，我们纳入了5岁时具有母体基因和神经发育信息的后代(DHA=316；对照=306)，并使用广义线性模型来评估FADS2 SNPs rs174602或rs174575与产前DHA之间的交互作用，用McCarthy儿童能力量表(MSCA)测量5年后神经发育。母体和子代的特征在组间相似。在基线时，母亲的平均年龄(±标准差)为26±5岁，受教育程度为12±4年。46%(46%)的孩子是女性。SNPs rs174602和rs174575的母系等位基因频率分别为0.37和0.33。SNP rs174602和干预组有显著差异(p为交互作用和t；0.05)，干预组儿童只有在TT(微小等位基因纯合子)的后代之间有更高的MSCA评分(DHA：均值±扫描电子显微镜=22.6±0.9vs对照=19.1±0.9，平均差值(Δ)=3.45；p=0.01)和记忆(DHA=27.9±1.1vs对照=23.7±1.1，Δ=4.26；p=0.02)。母亲FADS2 SNP rs174602在5岁时改变了产前DHA对认知发育的影响。目标人群的遗传构成的变异可能是产前补充DHA干预的一个重要因素。
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 1,094 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.
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