Whole-genome expression profiling of skeletal muscle reveals potential link between insulin resistance and diabetes in overweight West Africans

Wednesday, October 26, 2011 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center	NHGRI	ENDOC-11

Authors

• H Xu
• A Adeyemo
• A Elkahloun
• J Adeleye
• W Balogun
• H Huang
• J Zhou
• G Chen
• D Shriner
• C Adebamowo
• S Chandrasekharappa
• CN Rotimi

Abstract

Obesity is a major risk factor for type 2 diabetes (T2D). Little is known about changes in the transcriptome of skeletal muscle, a major tissue target of insulin action, in the early stages of obesity. Here, we examined genome-wide expression in skeletal muscle from West Africans (21 male non-diabetic adults from Ibadan, Nigeria). Seventy-one transcripts were differentially regulated (≥1.4-fold difference) between overweight (BMI≥25 kg/m2) and normal weight subjects (BMI<25 kg/m2). Principal component and cluster analyses showed separation of these two groups of subjects based on their gene expression profiles. Notably, 13/71 transcripts were in known risk genes (KCNQ5, HLA-DQA1, MEIS2, SPG7, PTGDS, TSPAN15, FAM78B, FAM102B, PMP22, SERPINA5, LPP, OSBPL3, and HLA-DPB1). SERPINA5 showed 1.9-fold increased expression in overweight subjects and positively correlated with the homeostatic model assessment of insulin resistance. Gene Set Enrichment Analysis identified the G-protein signaling pathway as the most significantly up-regulated pathway in overweight subjects (p<0.001, FDR=0.03). Compared to normal weight subjects, overweight subjects had changes in muscle gene expression in pathways dysregulated in T2D. To our knowledge, this study is the first to use expression profiling in skeletal muscle to identify genes underlying the associations among early weight gain, insulin resistance, and T2D in West Africans.

back to top