Maternal Lactase Polymorphism (rs4988235) Is Associated with Neural Tube Defects in Offspring in the National Birth Defects Prevention Study.
Maternal Lactase Polymorphism (rs4988235) Is Associated with Neural Tube Defects in Offspring in the National Birth Defects Prevention Study.
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DOI：
10.1093/jn/nxy246
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发表时间：
2019-02
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通讯作者：
Thanh T. Hoang;Y. Lei;L. E. Mitchell;Shreela V. Sharma;M. Swartz;D. Waller;R. Finnell;Renata H. Benjamin;M. Browne;M. Canfield;P. Lupo;Paige McKenzie;G. Shaw;A. Agopian
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作者：
Thanh T. Hoang;Y. Lei;L. E. Mitchell;Shreela V. Sharma;M. Swartz;D. Waller;R. Finnell;Renata H. Benjamin;M. Browne;M. Canfield;P. Lupo;Paige McKenzie;G. Shaw;A. Agopian
背景技术怀孕早期摄入足够的叶酸可以降低受神经管缺陷（NTD）影响的妊娠风险。然而，在叶酸摄入充足的女性的后代中观察到了 NTD。其中一些女性可能没有吸收足够的叶酸。由于乳糖酶缺乏会导致营养吸收不良，因此我们假设乳糖酶缺乏的女性后代患 NTD 的风险会增加。目的 我们检查了母体 rs4988235（一种乳糖酶缺乏遗传标记）与后代 NTD 之间的关联。方法 我们使用 1997-2009 年美国国家出生缺陷预防研究的数据进行了一项病例对照研究，仅限于非西班牙裔白人 (NHW) 和西班牙裔女性。病例是后代患有 NTD 的女性（n = 378 NHW，207 西班牙裔），对照是后代没有先天缺陷的女性（n = 461 NHW，165 西班牙裔）。使用逻辑回归按种族/民族分别进行分析。具有 CC 基因型的女性被归类为乳糖酶缺乏症。为了评估潜在的效果修改，根据乳糖摄入量、叶酸补充、膳食叶酸和饮食质量进行了分层分析。结果 在 NHW 女性中，与对照组相比，病例中乳糖酶缺乏的几率更大（OR：1.37；95% CI：1.02，1.82）。在西班牙裔女性中，病例中乳糖酶缺乏的几率明显低于对照组（OR：0.50，95％CI：0.33，0.77）。当按 NHW 女性的乳糖摄入量（摄入 ≥12 g 乳糖/1000 kcal 的女性的几率较高）和西班牙裔女性的膳食叶酸（关联方向相反）进行分层时，这种关联有所不同。当按叶酸补充或饮食质量分层时，这种关联没有差异。结论 我们的研究结果表明，母亲乳糖酶缺乏与后代 NTD 相关。然而，我们观察到种族/民族的影响方向相反，但无法明确解释。
BACKGROUND The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs. OBJECTIVE We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring. METHODS We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality. RESULTS Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality. CONCLUSIONS Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained.