Format

Send to

Choose Destination
Gene. 2017 Oct 20;632:50-58. doi: 10.1016/j.gene.2017.08.019. Epub 2017 Aug 26.

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

Author information

1
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
2
Department of Internal Medicine, Section on Endocrinology and Metabolism, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
3
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
4
Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
5
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
6
Department of Internal Medicine, Section on Endocrinology and Metabolism, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: sdas@wakehealth.edu.

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<0.01) with expression level of 1021 and 1875 adipose tissue transcripts, respectively, but none associated with total cholesterol or LDL-C levels. Serum HDL-C-associated transcripts were enriched for salient biological pathways, including branched-chain amino acid degradation, and oxidative phosphorylation. Genes in immuno-inflammatory pathways were activated among individuals with higher serum TRIG levels. We identified significant cis-regulatory SNPs (cis-eSNPs) for 449 serum lipid-associated transcripts in adipose tissue. The cis-eSNPs of 12 genes were nominally associated (p<0.001) with serum lipid level in genome wide association studies in Global Lipids Genetics Consortium (GLGC) cohorts. Allelic effect direction of cis-eSNPs on expression of 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.

KEYWORDS:

African Americans; Expression quantitative trait loci (eQTL); Gene expression profiling; Genotype; HDL-cholesterol; Triglyceride

PMID:
28844666
PMCID:
PMC5600164
DOI:
10.1016/j.gene.2017.08.019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center