An association study between SUFU gene polymorphisms and neural tube defects

Abstract

Neural tube defects (NTDs) in mammals are rooted in aberrant neural tube closure during early embryogenesis, which is caused by multiple environmental and genetic factors. The Sonic Hedgehog pathway is involved in the induction of the floor plate and participates in formation of the neural tube. Mutation of the suppressor of fused gene (SUFU), an essential repressor of Sonic Hedgehog signaling pathway, can result in NTDs. A case-control study was designed to compare the frequencies of the polymorphism at four sites in the SUFU gene in control and NTDs group, as well as in subtype groups, including anencephaly, spina bifida and encephalocele. We also explored the association between polymorphism and NTDs risk in a high prevalence population in China. Rs10786691, but not the other three SNPs, had an association between polymorphisms and NTDs. The heterozygous AG allele of rs10786691 was significantly related with NTDs and encephalocele (OR = 1.60, 95% CI: 1.04–2.48, p = 0.034; OR = 2.83, 95% CI: 1.07–7.47, p = 0.036). In female but not male fetuses, the AG genotype of rs10786691 increased the risk of NTDs (OR = 1.88, 95% CI: 1.03–3.41, p = 0.040). The SUFU rs10786691 A>G polymorphism may be a potential risk factor for NTDs and encephalocele in this high-risk population, but the association between the polymorphism and NTDs was probably influenced by gender.

KEYWORDS: :

• neural tube defects
• SUFU gene
• polymorphism
• Sonic Hdgehog pathway
• association study

Acknowledgements

The authors are grateful to all the participants in this study, particularly Jin Guo, Lihua Wu and Shaoyan Chang, and thank all obstetricians in the local hospital at Shanxi Province, as well as the pathologists in the Department of Pathology for the diagnosis. The authors also thank all the subjects and their family members for their cooperation in providing both clinical information and samples for the study. This work was supported by grants from the National Natural Science Fund of China, contract grant numbers 81000249 and 81150008, and by the Natural Science Fund of Beijing (13G20331/MG203).