Maternal single nucleotide polymorphisms in the fatty acid desaturase 1 and 2 coding regions modify the impact of prenatal supplementation with DHA on birth weight
Maternal single nucleotide polymorphisms in the fatty acid desaturase 1 and 2 coding regions modify the impact of prenatal supplementation with DHA on birth weight
复制标题
DOI：
10.3945/ajcn.115.121244
复制
发表时间：
2016-04-01
影响因子：
7.1
通讯作者：
Ramakrishnan, Usha
中科院分区：
文献类型：
--
作者：
Gonzalez-Casanova, Ines;Rzehak, Peter;Ramakrishnan, Usha
背景：脂肪酸脱饱和酶(FADS)基因的特异性单核苷酸多态(SNPs)影响酶的活性和效率，这些酶负责将多不饱和脂肪酸(PUFAs)转化为长链活性形式。与多不饱和脂肪酸转化缓慢相关的SNP在西班牙裔人群中的高患病率已被描述。目的：我们评估了在墨西哥妇女及其后代样本中，产前补充二十二碳六烯酸(DHA)对出生体重影响的异质性。设计：作为在墨西哥库埃纳瓦卡进行的随机对照试验的一部分，我们从654名通过分娩接受400 mg DHA/d或安慰剂的654名妇女的储存血液样本中获得关于母亲基因的信息。我们在FADS区域选择了4个标签SNP(rs174455、rs174556、rs174602和rs498793)进行分析。结果：平均出生体重+/-SD为3210+/-470g，年龄别体重(WAZ)为20.24+/-1.00。在出生体重方面没有意向治疗差异。SNP rs174602显示出显著的异质性(P=0.02)，干预组TT和TC等位基因携带者的后代体重高于安慰剂组(WAZ：-0.13+/-0.14和-0.20+/-0.08，而对照组分别为-0.55+/-0.15和-0.39+/-0.09)；Rs174602 CC纯合子的后代无显著差异(WAZ：干预组为-0.26+/-0.09，安慰剂组为-0.04+/-0.09)。在其他3个FADS SNPs中，我们没有表现出显著的异质性。结论：根据目标人群的基因构成，对产前补充DHA的不同反应可以解释补充DHA对出生体重影响的混合证据。这项试验在Clinicaltrials.gov上注册为NCT00646360。
Background: Specific single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene affect the activity and efficiency of enzymes that are responsible for the conversion of polyunsaturated fatty acids (PUFAs) into their long-chain active form. A high prevalence of SNPs that are associated with slow PUFA conversion has been described in Hispanic populations.Objective: We assessed the heterogeneity of the effect of prenatal supplementation with docosahexaenoic acid (DHA) on birth weight across selected FADS SNPs in a sample of Mexican women and their offspring.Design: We obtained information on the maternal genotype from stored blood samples of 654 women who received supplementation with 400 mg DHA/d or a placebo from weeks 18 to 22 of gestation through delivery as part of a randomized controlled trial conducted in Cuernavaca, Mexico. We selected 4 tag SNPs (rs174455, rs174556, rs174602, and rs498793) in the FADS region for analysis. We used an ANOVA to test for the heterogeneity of the effect on birth weight across each of the 4 SNPs.Results: The mean +/- SD birth weight was 3210 +/- 470 g, and the weight-for-age z score (WAZ) was 20.24 +/- 1.00. There were no intention-to-treat differences in birth weights. We showed significant heterogeneity by SNP rs174602 (P = 0.02); offspring of carriers of alleles TT and TC in the intervention group were heavier than those in the placebo group (WAZ: -0.13 +/- 0.14 and -0.20 +/- 0.08 compared with -0.55 +/- 0.15 and -0.39 +/- 0.09, respectively); there were no significant differences in offspring of rs174602 CC homozygotes (WAZ: -0.26 +/- 0.09 in the intervention group compared with -0.04 +/- 0.09 in the placebo group). We showed no significant heterogeneity across the other 3 FADS SNPs.Conclusion: Differential responses to prenatal DHA supplementation on the basis of the genetic makeup of target populations could explain the mixed evidence of the impact of DHA supplementation on birth weight. This trial was registered at clinicaltrials.gov as NCT00646360.