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Single-Nucleotide Polymorphisms in the KCNN3 Gene Associate With Preterm Birth

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Abstract

The objectives were to determine whether single-nucleotide polymorphisms (SNPs) in KCNN3 (encodes the small conductance calcium-activated potassium channel subfamily N, member 3), associate with preterm birth (PTB). In all, 602 preterm families with at least 1 preterm (< 37 weeks gestation) infant were studied: DNA from the infant and one or both parents were genotyped for 16 SNPs in KCNN3. A region of interest within KCNN3 was sequenced in 512 Caucasian non-Hispanic mothers (412 with preterm deliveries;100 who delivered at term). Family-based association testing was used for genotyping analysis; Fisher exact test was used for sequencing analysis. Six SNPs (rs1218585, rs4845396, rs12058931, rs1218568, rs6426985, and rs4845394) were associated with PTB (all Ps <.05). These variations were all located within the intronic region between exons 1 and 2. Maternal sequencing revealed an association of 3 SNPs with spontaneous PTB; rs1218585 (P =.007), rs1218584 (P =.05), and a novel SNP at chromosome1:153099353 (P =.02). Polymorphisms in KCNN3 are associated with PTB and investigation into the functional significance of these allelic changes is warranted.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Lori J. Day MD

  2. Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Kendra L. Schaa BS, Kelli K. Ryckman PhD, John M. Dagle MD, PhD & Jeffrey C. Murray MD

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

    Meg Cooper MS & Mary L. Marazita PhD

  4. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Golisano Children’s Hospital at Strong, Rochester, NY, USA

    Chin-To Fong MD

  5. Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Hyagriv N. Simhan MD

  6. Department of Obstetrics and Gynecology, Wake Forest University of Medicine, Winston-Salem, NC, USA

    David C. Merrill MD

  7. Department of Molecular Physiology & Biophysics, University of Iowa, 6-432 Bowen Science Building, Iowa City, IA, 52242, USA

    Sarah K. England PhD

Authors
  1. Lori J. Day MD
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  2. Kendra L. Schaa BS
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  3. Kelli K. Ryckman PhD
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  4. Meg Cooper MS
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  5. John M. Dagle MD, PhD
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  6. Chin-To Fong MD
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  7. Hyagriv N. Simhan MD
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  8. David C. Merrill MD
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  9. Mary L. Marazita PhD
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  10. Jeffrey C. Murray MD
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  11. Sarah K. England PhD
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Corresponding author

Correspondence to Sarah K. England PhD.

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Author’s Note

This study was conducted at the University of Iowa.

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Day, L.J., Schaa, K.L., Ryckman, K.K. et al. Single-Nucleotide Polymorphisms in the KCNN3 Gene Associate With Preterm Birth. Reprod. Sci. 18, 286–295 (2011). https://doi.org/10.1177/1933719110391277

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  • DOI: https://doi.org/10.1177/1933719110391277

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