Fiche publication
Date publication
novembre 2019
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MEYRE David
Tous les auteurs :
Meyre D, Andress EJ, Sharma T, Snippe M, Asif H, Maharaj A, Vatin V, Gaget S, Besnard P, Choquet H, Froguel P, Linton KJ
Lien Pubmed
Résumé
We sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252Val/rs147624636) in two heterozygous cases. The two CD36 mutation carriers had no family history of T2D and no clustering of cardio-metabolic complications. While the p.Pro191Leu mutation was found in 84 heterozygous carriers from five ethnic groups from the genome aggregation database (global frequency: 0.0297%, N = 141,321), only one European carrier of the p.Ala252Val mutation was identified (global frequency: 0.00040%, N = 125,523). The Pro191 and Ala252 amino acids were not conserved (74.8% and 68.9% across 131 animal species, respectively). In vitro experiments showed that the two CD36 mutant proteins are expressed and trafficked to the plasma membrane where they bind modified low-density-lipoprotein (LDL) cholesterol as normal. However, molecular modelling of the recent CD36 crystal structure showed that Pro191 was located at the exit/entrance gate of the lipid binding chamber and Ala252 was in line with the chamber. Overall, our data do not support a major contribution of CD36 rare coding mutations to T2D and its cardio-metabolic complications in the French population.
Mots clés
CD36 Antigens, genetics, Cell Membrane, genetics, Coronary Disease, genetics, Diabetes Mellitus, Type 2, genetics, Dyslipidemias, genetics, Genotype, Heterozygote, Humans, Lipoproteins, LDL, genetics, Metabolic Diseases, genetics, Mutation, Missense, genetics, Pulmonary Arterial Hypertension, genetics
Référence
Sci Rep. 2019 11 20;9(1):17123
