Oral clefts and maternal biomarkers of folate-dependent one-carbon metabolism in Utah.
Oral clefts and maternal biomarkers of folate-dependent one-carbon metabolism in Utah.
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DOI：
10.1002/bdra.20762
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发表时间：
2011-03
期刊：
影响因子：
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通讯作者：
Carey JC
中科院分区：
文献类型：
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作者：
Munger RG;Tamura T;Johnston KE;Feldkamp ML;Pfister R;Cutler R;Murtaugh MA;Carey JC
母亲叶酸摄入量和相关的生物标志物与口腔裂的风险不一致。在犹他州的一项研究中，测定了347例病例和469例对照的母亲血浆叶酸（PF）和红细胞叶酸（EF）、血浆吡哆醛-5 ′-磷酸（PLP;活性维生素B6）和总血浆同型半胱氨酸（tHcy）浓度。所有唇腭裂合并的风险，包括唇裂伴或不伴腭裂（CL/P）和单纯腭裂（CP），在最高PF四分位数比最低PF四分位数低65%（比值比[OR]，0.35; 95%置信区间[CI]，0.23 - 0.53; p趋势<0.001）。结果在具有孤立CL/P和CP的亚组中保持显著性（每个亚组的p趋势<0.001）。EF结果相似。在最高与最低PLP四分位数中，CP与其他畸形的风险较低（OR，0.25; 95%CI，0.07 - 0.95）;然而，PLP或tHcy没有其他相关性。病例和对照组之间平均生物标志物水平的差异随着分娩和母体采血之间间隔的增加而扩大。随着PF、EF和PLP四分位数的增加以及tHcy的降低，唇裂风险的降低在指数分娩和采血之间间隔较长与较短的母亲中更为明显。母亲血液叶酸浓度低与唇腭裂风险增加相关，病例组和对照组PF、EF、PLP和tHcy浓度的平均差异随时间推移而扩大。额外的机制研究是必要的，以阐明是否获得性或遗传性的叶酸代谢障碍在裂缝的病因学中发挥作用。
Maternal folate intake and related biomarkers have been inconsistently associated with a risk of oral clefts. Maternal concentrations of plasma folate (PF) and erythrocyte folate (EF), plasma pyridoxal-5′-phosphate (PLP; active vitamin B6) and total plasma homocysteine (tHcy) were measured in a Utah study with 347 cases and 469 controls. Risk of all clefts combined, including cleft lip with or without cleft palate (CL/P) and cleft palate only (CP), was 65% lower in the highest versus lowest PF quartile (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.23–0.53; p-trend < 0.001). Results remained significant in the subgroups with isolated CL/P and CP (p-trend < 0.001 in each). EF results were similar. In the highest versus lowest PLP quartile, risk of CP with other malformations was lower (OR, 0.25; 95% CI, 0.07–0.95); however, no other associations were significant for PLP or tHcy. Differences in mean bio-marker levels between cases and controls widened with an increasing interval between delivery and maternal blood collection. Decreased cleft risk with increasing quartiles of PF, EF, and PLP and decreasing tHcy was more apparent in mothers with a longer versus shorter interval between the index child delivery and blood collection. Low maternal blood folate concentration was associated with an increased risk of clefts, and the differences in mean case and control PF, EF, PLP, and tHcy concentrations widened over time. Additional mechanistic studies are warranted to elucidate whether an acquired or inherited disorder of folate metabolism plays a role in the etiology of clefts.