Ethnicity-specific Skeletal Muscle Transcriptional Signatures and Their Relevance to Insulin Resistance in Singapore

ABSTRACT: Context: Insulin resistance (IR) and obesity differ between ethnic groups in Singapore, with discordant rates of obesity and IR between several ethnic groups. However, the molecular basis underlying these differences are not clear. Objective: As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity and related traits. Design, Setting and Main Outcome measures: We integrated transcriptomic, genomic and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study. Patients: The study contains Chinese (n=63), Malay (n=51) and Asian-Indian (n=42) males, aged 21-40 years, without systemic diseases. Results: We found remarkable diversity in the SM transcriptome between the three ethnicities with >8,000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences between ethnicities were unique to SM. We identified a network of 46 genes that were specifically down-regulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene-clusters, four of which were also enriched for genes that were found in GWAS of metabolic traits and disease and correlated with variation in IR, obesity and related traits. Conclusion: We identified extensive gene expression changes in SM between the three Singaporean ethnicities, and report specific genes and molecular pathways that might underpin and explain the differences in IR between these ethnic groups.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117339 | GEO | 2019/07/23

REPOSITORIES: GEO