Placental genetic variations in circadian clock-related genes increase the risk of placental abruption

Qiu Chunfang, Gelaye Bizu, Denis Marie, Tadesse Mahlet G., Enquobahrie Daniel A., Ananth Cande V., Pacora Percy N., Salazar Manuel, Sanchez Sixto E., Williams Michelle A.. 2016. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption. International Journal of Molecular Epidemiology and Genetics, 7 (1) : 32-40.

Résumé : The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57-fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome.

Mots-clés Agrovoc : variation génétique, génome, épidémiologie, interactions biologiques, rythme circadien, gène, placenta, génomique

Classification Agris : L53 - Physiologie animale - Reproduction
L10 - Génétique et amélioration des animaux

Champ stratégique Cirad : Hors axes (2014-2018)

Auteurs et affiliations

• Qiu Chunfang, Swedish Medical Center (USA)
• Gelaye Bizu, Havard University (USA)
• Denis Marie, CIRAD-BIOS-UMR AGAP (FRA)
• Tadesse Mahlet G., Georgetown University (USA)
• Enquobahrie Daniel A., University of Washington (USA)
• Ananth Cande V., Columbia University (USA)
• Pacora Percy N., San Marcos University (PER)
• Salazar Manuel, San Marcos University (PER)
• Sanchez Sixto E., Universidad Peruana de Ciencias Aplicadas (PER)
• Williams Michelle A., Havard University (USA)

Source : Cirad-Agritrop (https://agritrop.cirad.fr/581316/)

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