Genetic predispositions for thromboembolism as a possible etiology for gastroschisis

Cardonick, Elyce; Broth, Richard; Kaufmann, M; Seaton, Jennifer; Henning, Doreen; Roberts, Nancy S.; Wapner, Ronald J.

doi:10.1016/j.ajog.2004.12.010

Cited by 18 publications

(14 citation statements)

References 13 publications

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“…Some variants showed a strong interaction with maternal smoking, which supports the hypothesis of a vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors [Torfs et al, ]. A second study found no association between variants in MTHFR , a gene related to homocysteine metabolism, and gastroschisis in 31 cases and 52 controls [Cardonick et al, ]. An additional study found no association between gastroschisis and AEBP1 variants, a gene that encodes an intracellular protein involved in pro‐inflammatory processes [Feldkamp et al, ].…”

Section: Introductionmentioning

confidence: 84%

“…There have been four studies of gene variants and gastroschisis over the past 10 years [Cardonick et al, ; Torfs et al, ; Feldkamp et al, ; Jenkins et al, ]. One investigated polymorphisms in 32 genes (representing enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal or epidermal strength) in a case‐control study of 57 cases of gastroschisis and 506 controls [Torfs et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Gene variants as risk factors for gastroschisis

Padula

Yang

Schultz

et al. 2016

American J of Med Genetics Pt A

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In a population‐based case‐control study in California of 228 infants, we investigated 75 genetic variants in 20 genes and risk of gastroschisis with regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We hypothesized that genes related to vascular compromise may interact with environmental factors to affect the risk of gastroschisis. Haplotypes were constructed for 75 gene variants using the HaploView program. Risk for gastroschisis associated with each gene variant was calculated for both the homozygotes and the heterozygotes, with the homozygous wildtypes as the referent. Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by logistic regression. We found 11 gene variants with increased risk and four variants with decreased risk of gastroschisis for heterozygous (ORh) or homozygous variants (ORv) genotypes. These included NOS3 (rs1036145) ORh = 0.4 (95% CI: 0.2–0.7); NOS3 (rs10277237) ORv = 2.7 (95% CI: 1.3–6.0); ADD1 (rs12503220) ORh = 2.9 (95% CI: 1.6–5.4), GNB3 (rs5443) ORh = 0.2 (95% CI: 0.1–0.5), ORv = 0.4 (95% CI: 0.2–0.9); ICAM1 (rs281428) ORv = 6.9 (95% CI: 2.1–22.9), ICAM1 (rs3093030) ORv = 2.6 (95% CI: 1.2–5.6); ICAM4 (rs281438) ORv = 4.9 (95% CI: 1.4–16.6), ICAM5 (rs281417) ORh = 2.1 (95% CI: 1.1–4.1), ORv = 4.8 (95% CI: 1.7–13.6); ICAM5 (rs281440) ORh = 23.7 (95% CI: 5.5–102.5), ORv = 20.6 (95% CI: 3.4–124.3); ICAM5 (rs2075741) ORv = 2.2 (95% CI: 1.1–4.4); NAT1 ORv = 0.3 (95% CI: 0.1–0.9). There were additional associations between several gene variants and gastroschisis among women aged 20–24 and among mothers with and without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further investigation in additional populations and with the interaction of additional environmental exposures. © 2016 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Gene variants as risk factors for gastroschisis

Padula

Yang

Schultz

et al. 2016

American J of Med Genetics Pt A

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“…Although the sample size is small, to our knowledge, this is the largest case‐control study examining genetic and non‐genetic risk factors for gastroschisis that has been completed to date. Five previous studies of genetic risk factors for gastroschisis included no more than 57 case families (whereas we included 170 case families) [Komuro et al, ; Cardonick et al, ; Torfs et al, ; Lammer et al, ; Feldkamp et al, ]. It is challenging to conduct genetic epidemiologic analyses on such a rare birth defect, especially one that disproportionally affects younger mothers who typically have lower participation in biospecimen collection.…”

Section: Discussionmentioning

confidence: 99%

Maternal smoking, xenobiotic metabolizing enzyme gene variants, and gastroschisis risk

Jenkins

Reefhuis

Gallagher

et al. 2014

American J of Med Genetics Pt A

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Maternal smoking during pregnancy is one proposed risk factor for gastroschisis, but reported associations have been modest, suggesting that differences in genetic susceptibility might play a role. We included 108 non-Hispanic white and 62 Hispanic families who had infants with gastroschisis, and 1147 non-Hispanic white and 337 Hispanic families who had liveborn infants with no major structural birth defects (controls) in these analyses. DNA was extracted from buccal cells collected from infants and mothers, and information on periconceptional smoking history was obtained from maternal interviews, as part of the National Birth Defects Prevention Study. We analyzed five polymorphisms in three genes that code for enzymes involved in metabolism of some cigarette smoke constituents (CYP1A1, CYP1A2, and NAT2). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) independently for maternal smoking and maternal and infant gene variants, and to assess joint associations of maternal smoking and maternal or infant gene variants with gastroschisis. In analyses adjusted for maternal age at delivery and stratified by maternal race-ethnicity, we identified three suggestive associations among 30 potential associations with sufficient numbers to calculate ORs: CYP1A1*2A for non-Hispanic white mothers who smoked periconceptionally (aOR=0.38, 95% CI 0.15-0.98), and NAT2*6 for Hispanic non-smoking mothers (aOR=2.17, 95% CI 1.12-4.19) and their infants (aOR=2.11, 95% CI 1.00-4.48). This analysis does not support the occurrence of effect modification between periconceptional maternal smoking and most of the xenobiotic metabolizing enzyme gene variants assessed.

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“…If gastroschisis has a vascular origin (early or later), then the variably increased incidence over the past decades should be due to some factor that increases the likelihood of vascular compromise, and it might be expected to have a concurrent effect on the rates of other lesions suggested to have a vascular origin, such as renal agenesis, small bowel atresia, or limb reduction defects (15). None of these lesions has shown such a pattern (16), and a search for an excess of thrombophilic factors in children with gastroschisis was negative (17). If one argues that gastroschisis is an early malformation arising at the time of the abdominal wall closure then any true association with later occurring bona fide vascular disruptions must be explained.…”

Section: Discussionmentioning

confidence: 99%

Escape of the yolk sac: a hypothesis to explain the embryogenesis of gastroschisis

et al. 2009

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Gastroschisis is a significant birth defect that in many countries has shown an increased prevalence in recent decades, and the change has affected primarily younger mothers. Despite numerous epidemiological studies no other consistent associated risk factor has been identified. In this paper we review the five main theories related to the pathogenesis of this malformation and outline the reasons why we think none fully explains the embryogenesis of gastroschisis. We briefly present some clinical observations we have made that we consider germane to the pathogenesis and outline a hypothesis that we think can account for the origins of this malformation. Our proposal is that the determining defect in gastroschisis is failure of the yolk sac and related vitelline structures to be incorporated into the umbilical stalk. Otherwise, ventral closure of the lateral abdominal walls occurs normally, thus orphaning the vitelline duct and yolk sac outside both the main body stalk and the abdominal wall. Thus, in addition to the umbilicus, the abdominal wall has a separate perforation through which the midpoint of the gut is attached to the exteriorized vitelline structures. This connection through the ventral wall prevents normal egress of the gut into the umbilical cord during the second month of development and acts as the egress point for the gut resulting in gastroschisis.

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Genetic predispositions for thromboembolism as a possible etiology for gastroschisis

Cited by 18 publications

References 13 publications

Gene variants as risk factors for gastroschisis

Gene variants as risk factors for gastroschisis

Maternal smoking, xenobiotic metabolizing enzyme gene variants, and gastroschisis risk

Escape of the yolk sac: a hypothesis to explain the embryogenesis of gastroschisis

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