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Maternal and fetal variation in genes of cholesterol metabolism is associated with preterm delivery

Journal of Perinatology volume 27, pages 672–680 (2007)Cite this article

Abstract

Objective:

To examine the contribution of variants in fetal and maternal cholesterol metabolism genes in preterm delivery (PTD).

Study Design:

A total of 40 single-nucleotide polymorphisms (SNPs) in 16 genes related to cholesterol metabolism were examined for 414 preterm infants (gestational ages 22 to 36 weeks; comprising 305 singletons and 109 twins) and at least 1 parent. Fetal effects were assessed using the transmission disequilibrium test (TDT) for each SNP, followed by a log linear model-based approach to utilize families with missing parental genotypes for those SNPs showing significance under TDT. Genetic variant effects were examined for a role in PTD, gestational age and birth weight. Maternal effects were estimated using a log linear model-based approach.

Result:

Among singleton gestations, suggestive association (P<0.01 without adjusting for multiple comparisons) was found between birth weight and fetal DHCR7 gene/SNP combinations (rs1630498, P=0.002 and rs2002064, P=0.003). Among all gestations, suggestive associations were found between PTD and fetal HMGCR (rs2303152, P=0.002) and APOA1 (rs 5070, P=0.004). The result for HMGCR was further supported by the log linear model-based test in the single births (P=0.007) and in all births (P=0.006). New associations (APOE and ABCA1) were observed when birth weight was normalized for gestational age suggesting independent effects of variants on birth weight separate from effects on PTD. Testing for maternally mediated genetic effects has identified suggestive association between ABCA1 (rs4149313, P=0.004) and decreased gestational age.

Conclusion:

Variants in maternal and fetal genes for cholesterol metabolism were associated with PTD and decreased birth weight or gestational age in this study. Genetic markers may serve as one mechanism to identify high-risk mothers and fetuses for targeted nutritional treatment and/or prevention of low birth weight or PTD.

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Acknowledgements

We thank, in particular, the families that participated in this study. The GCRC nurses at Iowa, Karen Johnson, Gretchen Cress, Nancy Krutzfield, Laura Knosp were essential in contacting, enrolling and sampling families. Kristin Orr and Cara Zimmerman were integral in sample organization. Sandy Daack-Hirsch assisted with consent protocols and Susie McConnell with manuscript preparation. The work was supported by NIH grant HD052953 and March of Dimes grant FY05-126.

Author information

Authors and Affiliations

  1. University of Iowa College of Medicine, Iowa City, IA, USA

    K M Steffen

  2. Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    M E Cooper

  3. National Institute of Environmental Health Science, Research Triangle Park, NC, USA

    M Shi

  4. Department of Pediatrics, University of Iowa, Iowa City, IA, USA

    D Caprau

  5. Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA, USA

    H N Simhan

  6. Department of Pediatrics, University of Iowa, Iowa City, IA, USA

    J M Dagle

  7. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    M L Marazita

  8. Department of Pediatrics, University of Iowa, Iowa City, IA, USA

    J C Murray

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Correspondence to J C Murray.

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Supplementary Information accompanies the paper on the Journal of Perinatology website (http://www.nature.com/jp)

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Steffen, K., Cooper, M., Shi, M. et al. Maternal and fetal variation in genes of cholesterol metabolism is associated with preterm delivery. J Perinatol 27, 672–680 (2007). https://doi.org/10.1038/sj.jp.7211806

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