A genome-wide and candidate gene association study of preterm birth in Korean pregnant women

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, it is crucial to predict and prevent PTB. Advancements enable the prediction and prevention of PTB using genetic approaches, especially by investigating its correlation with single nucleotide polymorphisms (SNPs). We aimed to identify impactive and relevant SNPs for the prediction of PTB via whole-genome sequencing analyses of the blood of 31 pregnant women with PTB (n = 13) and term birth (n = 18) who visited the Ewha Womans University Mokdong Hospital from November 1, 2018 to February 29, 2020. A genome-wide association study was performed using PLINK 1.9 software and 256 SNPs were selected and traced through protein-protein interactions. Moreover, a validation study by genotyping was performed on 60 other participants (preterm birth, n = 30; term birth, n = 30) for 25 SNPs related to ion channel binding and receptor complex pathways. Odds ratios were calculated using additive, dominant, and recessive genetic models. The risk of PTB in women with the AG allele of rs2485579 (gene name: RYR2) was significantly 4.82-fold increase, and the risk of PTB in women with the AG allele of rs7903957 (gene name: TBX5) was significantly 0.25-fold reduce. Our results suggest that rs2485579 (in RYR2) can be a genetic marker of PTB, which is considered through the association with abnormal cytoplasmic Ca2+ concentration and dysfunctional uterine contraction due to differences of RYR2 in the sarcoplasmic reticulum.