Genetic regulation of adipose tissue transcript expression is involved in modulating serum triglyceride and HDL-cholesterol

摘要

Abstract Dyslipidemia is a major contributor to the increased cardiovascular disease and mortality associated with obesity and type 2 diabetes. We hypothesized that variation in expression of adipose tissue transcripts is associated with serum lipid concentrations in African Americans (AAs), and common genetic variants regulate expression levels of these transcripts. Fasting serum lipid levels, genome-wide transcript expression profiles of subcutaneous adipose tissue, and genome-wide SNP genotypes were analyzed in a cohort of non-diabetic AAs ( N =250). Serum triglyceride (TRIG) and high density lipoprotein-cholesterol (HDL-C) levels were associated (FDR p MARCH2 , BEST1 and TMEM258 matched with effect direction of these SNP alleles on serum TRIG or HDL-C levels in GLGC cohorts. These data suggest that expressions of serum lipid-associated transcripts in adipose tissue are dependent on common cis-eSNPs in African Americans. Thus, genetically-mediated transcriptional regulation in adipose tissue may play a role in reducing HDL-C and increasing TRIG in serum. Highlights ? Derangement of transcript expression in adipose can modulate serum triglyceride (TRIG) and HDL-Cholesterol (HDL-C) level. ? In adipose immuno-inflammatory pathway genes were activated among individuals with higher serum TRIG and low HDL-C level. ? HDL-C-associated transcripts were enriched for branched chain amino acid catabolism, and oxidative phosphorylation genes. ? Expressions of serum lipid-associated transcripts in adipose are dependent on cis-regulatory polymorphisms (cis-eSNPs). ? Genetically-mediated transcriptional regulation in adipose may play a role in reducing HDL-C and increasing TRIG in serum.