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Mol Genet Genomic Med. 2019 Jun;7(6):e688. doi: 10.1002/mgg3.688. Epub 2019 Apr 9.

Maternal genetic markers for risk of celiac disease and their potential association with neural tube defects in offspring.

Author information

1
Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth School of Public Health, Houston, Texas.
2
Department of Molecular and Cellular Biology, Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas.
3
Department of Biostatistics and Data Science, UTHealth School of Public Health, Houston, Texas.
4
Congenital Malformations Registry, New York State Department of Health, Albany, New York.
5
Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Rensselaer, New York.
6
Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas.
7
Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas.
8
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.
9
Department of Pediatrics, Stanford University School of Medicine, Stanford, California.

Abstract

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.

KEYWORDS:

candidate genes; celiac disease; human leukocyte antigen; neural tube defects; pregnancy

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