Gene variants as risk factors for gastroschisis

Padula, Amy; Yang, Wei; Schultz, Kathleen; Tom, Lauren; Lin, Bin; Carmichael, Suzan L.; Lammer, Edward J.; Shaw, Gary M.

doi:10.1002/ajmg.a.37883

Cited by 18 publications

(16 citation statements)

References 26 publications

(34 reference statements)

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“…22 Previous reports revealed the effect of ICAM1 polymorphism on gastroschisis. 4,5 However, our study was unable to show an association between ICAM1 K469E polymorphism and gastroschisis risk, implying that the gastroschisis pathogenesis might be affected by several genetic risks, not only ICAM1 K469E variant. Furthermore, it seems likely that the gene-environment interaction has more impact on gastroschisis pathogenesis than a single genetic etiology.…”

Section: Discussioncontrasting

confidence: 60%

“…3 Recently, several studies have demonstrated an association between gastroschisis risk and common variants of the cell-cell interaction gene intracellular adhesion molecule 1 (ICAM1). 4,5 So far, there have been no such reports from the Asian region. Therefore, an additional study is warranted in Asia, particularly in Indonesia, because the ICAM1 K469E polymorphism frequency differs among ethnic groups, 6 and its effect on gastroschisis has never been determined to date.…”

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confidence: 99%

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ICAM1K469E Polymorphism Effect in Gastroschisis Patients

et al. 2018

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Objective: To evaluate the association between a common cell-cell interaction variant, intracellular adhesion molecule 1 (ICAM1) K469E, and gastroschisis risk in Indonesia. Summary of Background Data: Gastroschisis is a congenital disorder characterized by fetal intestines' extrusion outside the body. Several hypotheses have been proposed for gastroschisis, including an impairment in the normal attachment between umbilical cord and umbilical ring. Methods: A total of 48 infants with gastroschisis and 88 ethnicity-matched controls were involved in this study. The ICAM1 K469E polymorphism was analyzed using polymerase chain reaction-restriction fragment-length polymorphisms on genomic DNA. Results: The frequencies of genotypes for ICAM1 K469E in patients were KK, 30 of 48 (63%); KE, 17 of 48 (35%); and EE, 1 of 48 (2%), whereas their frequencies in controls were KK, 48 of 88 (55%); KE, 33 of 88 (37%); and EE, 7 of 88 (8%). Those frequencies were not significantly different between both groups (P ¼ 0.37) with an OR of 1.39 (95% CI, 0.68-2.85). The K469 allele had a frequency of 80% (77 of 96) in patients and 73% (129 of 176) in controls, and the frequency in patients was not significantly higher than that in controls (P ¼ 0.20), with an odds ratio of 1.48 (95% confidence interval, 0.81-2.70). In addition, the frequency of ICAM1 K469 allele in patients with maternal age younger than 25 years was

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Section: Discussioncontrasting

confidence: 60%

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confidence: 99%

ICAM1K469E Polymorphism Effect in Gastroschisis Patients

et al. 2018

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“…Unique to Utah, multigenerational pedigrees provide a rare opportunity to discover disease risk variants for any condition, including gastroschisis. Others have investigated specific gene variants based on known risk factors or animal studies of gastroschisis (Cardonick et al, ; Feldkamp, Bowles, & Botto, ; Jenkins et al, ; Padula et al, ; Torfs, Christianson, Iovannisci, Shaw, & Lammer, ). Padula et al () recently reported statistically significant associations with genes involved in cell–cell interactions ( ICAM1 , ICAM4 , ICAM5 ) and blood pressure ( NOS3 , ADD1 ).…”

Section: Introductionmentioning

confidence: 99%

Shared genomic segments in high‐risk multigenerational pedigrees with gastroschisis

Feldkamp

Krikov

Gardner

et al. 2019

Birth Defects Research

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Objectives: Gastroschisis remains an etiologic dilemma. We posit that an underlying genetic susceptibility either separately or coupled with a periconceptional environmental exposure stimulates an inflammatory response resulting in gastroschisis. To investigate the genetic link, we applied shared genomic segment (SGS) analysis, a novel approach to discover chromosomal segments that inherit in high-risk multigenerational pedigrees. Methods: We studied pedigrees containing distantly related children with gastroschisis originating from a common ancestor. We used the Illumina OmniExpress genotyping array with >700,000 SNPs. Samples from 40 affected children in 13 pedigrees (≥3 affected children) were genotyped to generate the high-density SNP data necessary to perform SGS analysis. Assessment of significance in SGS was determined empirically using simulations based on precise pedigree structure and modeling linkage disequilibrium (LD) for SNPs in the general population to properly account for genetic architecture. The LD model was estimated from the 1000 Genome Project using the same set of SNPs. Genome-wide significance thresholds were determined for each pedigree. Results: We identified six pedigrees that contained genome-wide statistically significant SGS regions inherited from a common founder. These regions were different in each pedigree, all contained immune pathway genes. Discussion: The genome-wide significant regions support a genetic susceptibility for gastroschisis. The regions are compelling candidates for regionally focused genome sequencing, enabling the discovery of coding or noncoding (e.g., regulatory) risk variants, the latter of which are unlikely to be found using conventional exomic/genefocused approaches. This technique provides a comprehensive and focused genomic interrogation that will help to advance our understanding of gastroschisis. K E Y W O R D Sgastroschisis, genetics, high-risk multigenerational pedigrees

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“…Also maternal exposure to environmental factors, such as smoking during pregnancy as well as vitamin use, in white and Hispanic mothers of different age groups has been studied. The result of this study was that a few gene variants may be associated with a higher risk for gastroschisis, but further studies are needed (Padula et al, ).…”

Section: Discussionmentioning

confidence: 88%