母体遗传标志物与乳糜泻风险及其与后代神经管缺陷的潜在关联。
Maternal genetic markers for risk of celiac disease and their potential association with neural tube defects in offspring.
机构信息
Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth School of Public Health, Houston, Texas.
Department of Molecular and Cellular Biology, Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas.
出版信息
Mol Genet Genomic Med. 2019 Jun;7(6):e688. doi: 10.1002/mgg3.688. Epub 2019 Apr 9.
BACKGROUND
We examined the association between the maternal genotype for celiac disease-associated variants and risk of neural tube defects (NTDs).
METHODS
We conducted a case-control study, using data from the National Birth Defects Prevention Study. We evaluated 667 cases (women with an offspring with NTD) and 743 controls (women with an offspring without a birth defect). We classified women as having low, intermediate, or high risk of celiac disease based on human leukocyte antigen (HLA) variants. We used logistic regression to assess the relationship between HLA celiac risk group (low, intermediate, high) and risk of NTDs. Fifteen non-HLA variants (identified from genome-wide association studies of celiac disease) were individually evaluated and modeled additively.
RESULTS
There was no association between HLA celiac risk group and NTDs (intermediate vs. low risk: aOR, 1.0; 95% CI, 0.8-1.3; high vs. low risk: aOR, 0.8; 95% CI, 0.5-1.3). Of the fifteen non-HLA variants, we observed five significant associations after accounting for multiple comparisons. Three negative associations were observed with rs10903122, rs13314993, rs13151961 (aOR range: 0.69-0.81), and two positive associations were observed with rs13003464 and rs11221332 (aOR range: 1.27-1.73).
CONCLUSION
If confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs.
背景
我们研究了乳糜泻相关变异的母体基因型与神经管缺陷（NTD）风险之间的关联。
方法
我们进行了一项病例对照研究，使用了国家出生缺陷预防研究的数据。我们评估了 667 例病例（子女患有 NTD 的女性）和 743 例对照（子女无出生缺陷的女性）。我们根据人类白细胞抗原（HLA）变体将女性分为乳糜泻低、中、高风险组。我们使用逻辑回归评估 HLA 乳糜泻风险组（低、中、高）与 NTD 风险之间的关系。我们分别评估并以累加方式模拟了 15 个非 HLA 变体（从乳糜泻全基因组关联研究中确定）。
结果
HLA 乳糜泻风险组与 NTD 之间没有关联（中危与低危相比：aOR，1.0；95%CI，0.8-1.3；高危与低危相比：aOR，0.8；95%CI，0.5-1.3）。在十五个非 HLA 变体中，我们观察到在进行多次比较后有五个具有显著相关性。rs10903122、rs13314993、rs13151961 与三个负相关（aOR 范围：0.69-0.81），rs13003464 和 rs11221332 与两个正相关（aOR 范围：1.27-1.73）。
结论
如果得到证实，我们的结果表明与乳糜泻相关的母体变异可能与 NTD 风险有关。
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