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Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

ABSTRACT: 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.

SUBMITTER: Meyre D

PROVIDER: S-EPMC6868229 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

Meyre David D Andress Edward J EJ Sharma Tanmay T Snippe Marjolein M Asif Hamza H Maharaj Arjuna A Vatin Vincent V Gaget Stefan S Besnard Philippe P Choquet Hélène H Froguel Philippe P Linton Kenneth J KJ

Scientific reports 20191120 1

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 mut ...[more]

PMID: 31748580

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Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

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Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

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