Previous miscarriages and GLI2 are associated with anorectal malformations in offspring.
Hum Reprod
; 32(2): 299-306, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-28057877
ABSTRACT
STUDY QUESTION Are anorectal malformations (ARMs) associated with previous miscarriages or single nucleotide polymorphisms (SNPs) in the Bone Morphogenetic Protein 4 (BMP4) and GLI family zinc finger 2 (GLI2) genes? SUMMARY ANSWER The SNP rs3738880 in GLI2 and miscarriages were associated with ARM, especially in patients with multiple congenital anomalies (MCA). WHAT IS KNOWN ALREADY ARM are one of the most common birth defects of the gastrointestinal tract. The etiology is likely to be multifactorial, involving both environmental and genetic factors. SNPs in BMP4 and GLI2 genes were associated with ARM in non-Caucasian populations. During a patient information day, several mothers of ARM patients reported their concerns about previous miscarriages. STUDY DESIGN, SIZE, DURATION A case-control study was performed among 427 ARM patients and 663 population-based controls. PARTICIPANTS/MATERIALS, SETTING, METHODS:
We examined the associations of ARM with SNPs in GLI2 and BMP4 using DNA samples of the children and associations with previous miscarriages using parental questionnaires. In addition, gene-gene and gene-environment interaction analyses were performed. MAIN RESULTS AND THE ROLE OF CHANCE The SNP rs3738880 in GLI2 was associated with ARM, especially in patients with MCA (homozygous GG-genotype odds ratio (OR) 2.1; 95% CI 1.2, 3.7). We identified previous miscarriages as a new risk factor for ARM, especially when occurring in the pregnancy directly preceding the index pregnancy and in patients with MCA (OR 2.1; 95% CI 1.3, 3.5). No association with rs17563 in BMP4, nor gene-gene or gene-environment interactions were found. LIMITATIONS, REASONS FOR CAUTION The possibility of recall errors for previous miscarriage, but we expect these errors to be limited, as a miscarriage is a major life event. In addition, potential misclassification regarding miscarriages and stillbirth, but sensitivity analyses showed that this did not influence our results. WIDER IMPLICATIONS OF THEFINDINGS:
This study showed associations of ARM with rs3738880 in GLI2 and with previous miscarriages. Both associations were stronger in patients with MCA, showing the importance of stratifying the analyses by patients with isolated ARM or MCA. STUDY FUNDING/COMPETING INTERESTS This study was funded by the Radboudumc. The authors have no conflict of interest to disclose.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Aborto Habitual
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Malformações Anorretais
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Proteína Gli2 com Dedos de Zinco
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Newborn
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Pregnancy
Idioma:
En
Revista:
Hum Reprod
Assunto da revista:
MEDICINA REPRODUTIVA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Holanda