Genetic variants conferring susceptibility to gastroschisis: a phenomenon restricted to the interaction with the environment?
Genes involved in gastroschisis have shown a strong interaction with environmental factors. However, less is known about its influence. We aimed to systematically review the genetic associations of gastroschisis, to summarize whether its genetic susceptibility has been restricted to the interaction with the environment, and to identify significant gaps that remain for consideration in future studies.
Genetic association studies of gastroschisis published 1980–2017 (PubMed/MEDLINE) were independently searched by two reviewers. Significant SNP–gastroschisis associations were grouped into crude and stratified risks, whereas SNPs were assessed from two or more independent studies. Frequencies, odds ratios, and 95% confidence intervals were pooled using descriptive analysis and Chi-square test accounting for heterogeneity.
Seven eligible articles capturing associations of 14 SNPs from 10 genes for crude risk (including 10 and 4 SNPs with increased and decreased risk, respectively) and 30 SNPs from 14 genes for stratified risk in gastroschisis (including 37 and 14 SNPs with increased and decreased risk, respectively) were identified (Fisher’s exact test, P = 0.438). The rs4961 (ADD1), rs5443 (GNB3), rs1042713, and rs1042714 (ADRB2) were significantly associated with gastroschisis.
Genetic susceptibility in gastroschisis is not restricted to the interaction with the environment and should not be too narrowly focused on environmental factors. We found significant associations with four SNPs from three genes related to blood pressure regulation, which supports a significant role of vascular disruption in the pathogenesis of gastroschisis. Future studies considering gene–gene or gene–environmental interactions are warranted for better understanding the etiology of gastroschisis.
KeywordsGastroschisis Gene Genetics Single-nucleotide polymorphism Population-based
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Conflict of interest
The authors declared no potential conflicts of interest and received no financial support with respect to the research, authorship, and/or publication of this article.
This article does not contain any studies with human participants or animals performed by any of the authors and did not require formal ethical approval.
No form of informed consent was required.
- 1.Mastroiacovo P (2014) International Clearinghouse for Birth Defects Monitoring Systems, Annual Report 2014. International Centre of Birth Defects, RomeGoogle Scholar
- 12.Salinas-Torres VM, Salinas-Torres RA, Cerda-Flores RM, Martínez-de-Villarreal LE (2017) Evaluation of familial factors in a Mexican population-based setting with gastroschisis: further evidence for an underlying genetic susceptibility. J Pediatr Surg. https://doi.org/10.1016/j.jpedsurg.2017.08.021 PubMedGoogle Scholar