Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population

Objective: To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. Study Design: Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. Result: Fetal association with PTB was found in the progesterone receptor ( PGR , rs1942836; P =0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 ( KCNN3 , rs883319; P =0.01). Gestational age associated with PTB in PGR rs1942836 at 32–36 weeks ( P =0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. Conclusion: This study replicates single locus fetal associations with PTB in PGR , maternal association in KCNN3 , and demonstrates possible effects for divergent racial admixture on PTB.