Reproductive Sciences

, Volume 18, Issue 3, pp 286–295 | Cite as

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

  • Lori J. Day
  • Kendra L. Schaa
  • Kelli K. Ryckman
  • Meg Cooper
  • John M. Dagle
  • Chin-To Fong
  • Hyagriv N. Simhan
  • David C. Merrill
  • Mary L. Marazita
  • Jeffrey C. Murray
  • Sarah K. EnglandEmail author
Original Articles


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.


KCNN3 SK3 preterm birth ion channel 


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Copyright information

© Society for Reproductive Investigation 2011

Authors and Affiliations

  • Lori J. Day
    • 1
  • Kendra L. Schaa
    • 2
  • Kelli K. Ryckman
    • 2
  • Meg Cooper
    • 3
  • John M. Dagle
    • 2
  • Chin-To Fong
    • 4
  • Hyagriv N. Simhan
    • 5
  • David C. Merrill
    • 6
  • Mary L. Marazita
    • 3
  • Jeffrey C. Murray
    • 2
  • Sarah K. England
    • 7
    Email author
  1. 1.Department of Obstetrics and GynecologyUniversity of Iowa Carver College of MedicineIowa CityUSA
  2. 2.Department of PediatricsUniversity of Iowa Carver College of MedicineIowa CityUSA
  3. 3.Department of Oral Biology, Center for Craniofacial and Dental GeneticsUniversity of PittsburghPittsburghUSA
  4. 4.Department of PediatricsUniversity of Rochester School of Medicine and Dentistry, Golisano Children’s Hospital at StrongRochesterUSA
  5. 5.Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens HospitalUniversity of Pittsburgh Medical CenterPittsburghUSA
  6. 6.Department of Obstetrics and GynecologyWake Forest University of MedicineWinston-SalemUSA
  7. 7.Department of Molecular Physiology & BiophysicsUniversity of IowaIowa CityUSA

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