Alba Rodriguez-Rius1, Sonia Lopez1, Angel Martinez-Perez1, Juan Carlos Souto2, Jose Manuel Soria1. 1. From the Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain (A.R.-R., S.L., A.M.-P., J.M.S.). 2. Unit of Thrombosis and Hemostasis, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (J.C.S.).
Abstract
OBJECTIVE: Venous thrombosis (VT) is a complex condition with a highly heritable genetic component that predisposes one to its development. Certain microRNAs (miRNAs) might be used as biomarkers of VT, but few studies have examined miRNA expression in this respect. The aim of the present work was to identify a plasma miRNA profile associated with VT. Approach and Results: miRNAs were analyzed by quantitative polymerase chain reaction in plasma samples from members of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) population (n=935). A discovery phase involving the screening of 752 miRNAs from a subset of 104 GAIT-2 subjects was followed by an internal validation phase in which the selected miRNAs were quantified in the whole GAIT-2 population. In the discovery phase, 16 miRNAs were selected, including 9 associated with VT and 7 that correlated with an intermediate phenotype of VT. In the next phase, 4 miRNAs were validated as differentially expressed (false discovery rate, <0.1) in VT: hsa-miR-126-3p, hsa-miR-885-5p, hsa-miR-194-5p, and hsa-miR-192-5p. The 4 miRNAs each returned a significant (P<0.05) odds ratio for VT (range of 1.3-1.8). A risk model including the 4 miRNAs, age, and sex returned an area under the receiver operating characteristic curve of 0.77. Moreover, all 4 miRNAs showed significant correlations with intermediate phenotypes of VT (eg, protein S and factor VII). The targets of the miRNAs in the blood coagulation pathway and their interactions are also discussed. CONCLUSIONS: The present results suggest a 4-miRNA plasma profile associated with VT is of potential use in predicting the risk of this condition.
OBJECTIVE:Venous thrombosis (VT) is a complex condition with a highly heritable genetic component that predisposes one to its development. Certain microRNAs (miRNAs) might be used as biomarkers of VT, but few studies have examined miRNA expression in this respect. The aim of the present work was to identify a plasma miRNA profile associated with VT. Approach and Results: miRNAs were analyzed by quantitative polymerase chain reaction in plasma samples from members of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) population (n=935). A discovery phase involving the screening of 752 miRNAs from a subset of 104 GAIT-2 subjects was followed by an internal validation phase in which the selected miRNAs were quantified in the whole GAIT-2 population. In the discovery phase, 16 miRNAs were selected, including 9 associated with VT and 7 that correlated with an intermediate phenotype of VT. In the next phase, 4 miRNAs were validated as differentially expressed (false discovery rate, <0.1) in VT: hsa-miR-126-3p, hsa-miR-885-5p, hsa-miR-194-5p, and hsa-miR-192-5p. The 4 miRNAs each returned a significant (P<0.05) odds ratio for VT (range of 1.3-1.8). A risk model including the 4 miRNAs, age, and sex returned an area under the receiver operating characteristic curve of 0.77. Moreover, all 4 miRNAs showed significant correlations with intermediate phenotypes of VT (eg, protein S and factor VII). The targets of the miRNAs in the blood coagulation pathway and their interactions are also discussed. CONCLUSIONS: The present results suggest a 4-miRNA plasma profile associated with VT is of potential use in predicting the risk of this condition.
Authors: Alba Rodriguez-Rius; Angel Martinez-Perez; Sonia López; Maria Sabater-Lleal; Juan Carlos Souto; José Manuel Soria Journal: Epigenetics Date: 2020-06-24 Impact factor: 4.528
Authors: Marion Pilard; Estelle L Ollivier; Virginie Gourdou-Latyszenok; Francis Couturaud; Catherine A Lemarié Journal: Front Cardiovasc Med Date: 2022-04-21
Authors: David de Gonzalo-Calvo; Iván D Benítez; Lucía Pinilla; Amara Carratalá; Anna Moncusí-Moix; Clara Gort-Paniello; Marta Molinero; Jessica González; Gerard Torres; María Bernal; Silvia Pico; Raquel Almansa; Noelia Jorge; Alicia Ortega; Elena Bustamante-Munguira; José Manuel Gómez; Milagros González-Rivera; Dariela Micheloud; Pablo Ryan; Amalia Martinez; Luis Tamayo; César Aldecoa; Ricard Ferrer; Adrián Ceccato; Laia Fernández-Barat; Ana Motos; Jordi Riera; Rosario Menéndez; Dario Garcia-Gasulla; Oscar Peñuelas; Antoni Torres; Jesús F Bermejo-Martin; Ferran Barbé Journal: Transl Res Date: 2021-05-25 Impact factor: 7.012