Genetic Regulation of Enoyl-CoA Hydratase Domain-Containing 3 in Adipose Tissue Determines Insulin Sensitivity in African Americans and Europeans

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Insulin resistance (IR) is a harbinger of type 2 diabetes (T2D) and partly determined by genetic factors. However, genetically regulated mechanisms of IR remain poorly understood. Using gene expression, genotype, and insulin sensitivity data from the African American Genetics of Metabolism and Expression (AAGMEx) cohort, we performed transcript-wide correlation and expression quantitative trait loci (eQTL) analyses to identify IR-correlated cis -regulated transcripts ( cis -eGenes) in adipose tissue. These IR-correlated cis -eGenes were tested in the European ancestry individuals in the Metabolic Syndrome in Men (METSIM) cohort for trans-ethnic replication. Comparison of Matsuda index-correlated transcripts in AAGMEx with the METSIM study identified significant correlation of 3,849 transcripts, with concordant direction of effect for 97.5% of the transcripts. cis -eQTL for 587 Matsuda index-correlated genes were identified in both cohorts. Enoyl-CoA hydratase domain-containing 3 ( ECHDC3 ) was the top-ranked Matsuda index-correlated cis -eGene. Expression levels of ECHDC3 were positively correlated with Matsuda index, and regulated by cis -eQTL, rs34844369 being the top cis -eSNP in AAGMEx. Silencing of ECHDC3 in adipocytes significantly reduced insulin-stimulated glucose uptake and Akt Ser 473 phosphorylation. RNA sequencing analysis identified 691 differentially expressed gen

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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