Abstract
Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify associations of spontaneous PTB with genetic variants, exposures, and interactions between and within them. We carried out a retrospective case–control study including parental sociodemographic and obstetric data, and fetal genetic variants. We sequenced the coding and flanking regions of five candidate genes from the placental blood cord of 69 preterm newborns and 61 at term newborns. We identify the characteristics with the greatest predictive power of PTB using penalized regressions, in which we include exposures (E), genetic variants (G), and two-way interactions. Few prenatal visits (< 5) was the main predictor of PTB from 26 G, 35 E, 299 G × G, 564 E × E, and 875 G × E evaluated terms. Within the fetal genetic characteristics, we observed associations of rs4845397 (KCNN3, allele T) variant; G × G interaction between rs12621551 (COL4A3, allele T) and rs73993878 (COL4A3, allele A), which showed sensitivity to anemia; and G × G interaction between rs11680670 (COL4A3, allele T) and rs2074351 (PON1, allele A), which showed sensitivity to vaginal discharge. The results of this exploratory study suggest that social disparities and metabolic pathways linked to uterine relaxation, inflammation/infections, and collagen metabolism would be involved in PTB etiology. Future studies with a larger sample size are necessary to confirm these findings and to analyze a greater number of exposures.
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Acknowledgements
The authors want to thank Mrs. Mariana Piola and Alejandra Mariona.
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This work was supported by Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-MINCyT), grants: PICT-2018–4275 to JSLC and PICT-2018–4285 to LGG; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Instituto Nacional de Genética Médica Populacional (INAGEMP) [Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) grant 465549/2014–4; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), grant 88887.136366/2017–00; and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), grant 17/2551–0000521-0]; and from Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA), grant 17–0445. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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DEE, LGG, and JSLC contributed in the conception of the study; CS, VC, JSLC, and LGG contributed in the acquisition of data; VC, HBK, MR, HC, RU, LGG, DEE, and SLH contributed in the review and curation of data; LGG, DRM, ABON, and ACBF contributed in DNA sequencing; DEE, LGG, JSLC, FAP, JAG, MRS, and JR contributed in the analysis of data. All authors contributed in the drafting of the manuscript, critical revision for important intellectual content, and final approval of the published version.
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Elias, D.E., Santos, M.R., Campaña, H. et al. Genes, exposures, and interactions on preterm birth risk: an exploratory study in an Argentine population. J Community Genet 13, 557–565 (2022). https://doi.org/10.1007/s12687-022-00605-z
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DOI: https://doi.org/10.1007/s12687-022-00605-z