Shaw Gary M, Lammer Edward J, Zhu Huiping, Baker Mei Wang, Neri Eric, Finnell Richard H
March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Oakland, California 94606, USA.
Am J Med Genet. 2002 Feb 15;108(1):1-6. doi: 10.1002/ajmg.10195.
Women who consume folic acid in early pregnancy reduced their risks for delivering offspring with neural tube defects (NTDs). The underlying process by which folic acid facilitated this risk reduction is unknown. Investigating genetic variation that influences cellular absorption, transport, and metabolism of folate will help fill this data gap. We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1). Using data from a California population-based case control interview study (1989-1991 birth cohorts), we investigated whether spina bifida risk was influenced by an interaction between a polymorphism of infant RFC1 at nucleotide 80 (A80G) and maternal periconceptional use of vitamins containing folic acid. Allelic variants of RFC1 were determined by genotyping 133 live-born spina bifida case infants and 188 control infants. The percentages of case infants with the A80/A80, G80/G80, and G80/A80 genotypes were 27.2%, 28.0%, and 44.7%, respectively. The percentages of control infants were similar: 26.1%, 29.3%, and 44.7%. Odds ratios of 1.0 (95% confidence interval 0.5-2.0) for the G80/G80 genotype and 1.1 (0.6-2.0) for the G80/A80 genotype were observed relative to the A80/A80 genotype. Among mothers who did not use vitamins, spina bifida risk was 2.4 (0.8-6.9) for infants with genotype G80/G80 compared to those with A80/A80 genotype. Among mothers who did use vitamins, the risk was 0.5 (0.1-3.1) for infants with the G80/G80 genotype. Although this study did not find an increased spina bifida risk for infants who were heterozygous or homozygous for RFC1 A80G, it did reveal modest evidence for a gene-nutrient interaction between infant homozygosity for the RFC1 G80/G80 genotype and maternal periconceptional intake of vitamins containing folic acid on the risk of spina bifida.
怀孕早期摄入叶酸的女性降低了生出患有神经管缺陷（NTDs）后代的风险。叶酸降低这种风险的潜在机制尚不清楚。研究影响叶酸细胞吸收、转运和代谢的基因变异将有助于填补这一数据空白。我们将研究重点放在一个参与叶酸转运的候选基因——还原型叶酸载体1（RFC1）上。利用来自加利福尼亚州一项基于人群的病例对照访谈研究（1989 - 1991年出生队列）的数据，我们调查了婴儿RFC1第80位核苷酸多态性（A80G）与母亲孕期前后使用含叶酸维生素之间的相互作用是否会影响脊柱裂风险。通过对133名存活的脊柱裂病例婴儿和188名对照婴儿进行基因分型来确定RFC1的等位基因变异。病例婴儿中A80/A80、G80/G80和G80/A80基因型的百分比分别为27.2%、28.0%和44.7%。对照婴儿的百分比相似：分别为26.1%、29.3%和44.7%。相对于A80/A80基因型，G80/G80基因型的优势比为1.0（95%置信区间0.5 - 2.0），G80/A80基因型的优势比为1.1（0.6 - 2.0）。在未使用维生素的母亲中，与A80/A80基因型婴儿相比，G80/G80基因型婴儿的脊柱裂风险为2.4（0.8 - 6.9）。在使用维生素的母亲中，G80/G80基因型婴儿的风险为0.5（0.1 - 3.1）。尽管这项研究没有发现RFC1 A80G杂合或纯合的婴儿脊柱裂风险增加，但它确实揭示了适度的证据，表明婴儿RFC1 G80/G80基因型纯合与母亲孕期前后摄入含叶酸维生素之间存在基因 - 营养素相互作用，影响脊柱裂风险。
