Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty

Anguita-Ruiz, A ; Gonzalez-Gil, EM ; Rupérez, Azahara I. (Universidad de Zaragoza) ; Llorente-Cantarero, FJ ; Pastor-Villaescusa, B ; Alcala-Fdez, J ; Moreno, LA ; Gil, A ; Gil-Campos, M ; Bueno, Gloria (Universidad de Zaragoza) ; Leis, R ; Aguilera, CM

Resumen: Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic variants have been widely associated with obesity in children populations. The implication of such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the prediction and pharmacological management of obesity in Spanish children, further investigating its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted on genetics data from three well-characterized children populations (composed of 574, 96 and 124 individuals), following both cross-sectional and longitudinal designs, expanding childhood and puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI Z-Score (B = 1.56, SE = 0.27 andp-value = 1.90 x 10(-8)), and that could be used as a good predictor of obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not associated with cardio-metabolic comorbidities in children and that certain environmental factors interact with the genetic predisposition to the disease. Finally, according to the results derived from a weight-reduction metformin intervention in children with obesity, we discarded the utility of the pGRS as a pharmacogenetics marker of metformin response.

Idioma: Inglés

DOI: 10.3390/jcm9061705

Año: 2020

Publicado en: Journal of Clinical Medicine 9, 6 (2020), 1705 [23 pp.]
ISSN: 2077-0383

Factor impacto JCR: 4.241 (2020)

Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 39 / 169 = 0.231 (2020) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/i-PFIS-IFI17-00048
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI11-02042
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI11-02059
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI16-00871
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI16-01301
Financiación: info:eu-repo/grantAgreement/ES/MSCBS/EC10-056
Financiación: info:eu-repo/grantAgreement/ES/MSCBS/EC10-227
Financiación: info:eu-repo/grantAgreement/ES/MSCBS/EC10-243
Financiación: info:eu-repo/grantAgreement/ES/MSCBS/EC10-281

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Enfermería (Dpto. Fisiatría y Enfermería)
Área (Departamento): Área Pediatría (Dpto. Microb.Ped.Radio.Sal.Pú.)