Candidate gene linkage approach to Identify DNA variants that predispose to preterm birth

Department of Pediatrics, University of Iowa, Iowa City, IA.
Pediatric Research (Impact Factor: 2.31). 11/2012; 73(2). DOI: 10.1038/pr.2012.166
Source: PubMed


To identify genetic variants contributing to preterm birth using a linkage candidate gene approach.

We studied 99 single nucleotide polymorphisms for 33 genes in 257 families with preterm births segregating. Nonparametric and parametric analyses were used. Premature infants and mothers of premature infants were defined as affected cases in independent analyses.

Analyses with the infant as the case identified two genes with evidence of linkage: CRHR1 (p=0.0012) and CYP2E1 (p=0.0011). Analyses with the mother as the case identified four genes with evidence of linkage: ENPP1 (p=0.003), IGFBP3 (p=0.006), DHCR7 (p=0.009), and TRAF2 (p=0.01). DNA sequence analysis of the coding exons and splice sites for CRHR1 and TRAF2 identified no new likely etiologic variants.

These findings suggest the involvement of six genes acting through the infant and/or the mother in the etiology of preterm birth.

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Available from: John M Dagle, Feb 11, 2014
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    • "So far, the analysis of rare variants associated with preterm birth has been limited. In one study exploiting candidate gene linkage for 33 genes in 257 families, nonparametric and parametric analyses performed on 99 SNPs in premature infants and mothers of premature infants resulted in the identification of a moderate association with preterm birth of corticotropin releasing hormone receptor 1 (CRHR1) and cytochrome P450 2E1 (CYP2E1) in affected infants, and with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), insulin-like growth factor binding protein 3 (IGFBP3), TNF receptor-associated factor 2 (TRAF2) and 7-dehydrocholesterol reductase (DHCR7) in mothers [61]. DNA sequence analysis was performed for CRHR1 and TRAF2 to detect novel potentially causative mutations, but no new variants were detected [61]. "
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