Single-nucleotide polymorphisms in the KCNN3 gene associate with preterm birth.
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.
1Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Lori J
LJ
Day
Kendra L
KL
Schaa
Kelli K
KK
Ryckman
Meg
M
Cooper
John M
JM
Dagle
Chin-To
CT
Fong
Hyagriv N
HN
Simhan
David C
DC
Merrill
Mary L
ML
Marazita
Jeffrey C
JC
Murray
Sarah K
SK
England
D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*
C406328:KCNN3 protein, human; D051640:Small-Conductance Calcium-Activated Potassium Channels; D004247:DNA
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