Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome

Abstract

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors for all-cause mortality, cardiovascular disease, and cancer. Identifying epigenetic alterations associated with MetS in African Americans (AAs) and Whites may provide insight into genes that influence its differential health outcomes. We examined DNA methylation (DNAm) and performed an epigenome-wide association study (EWAS) of MetS among AAs and Whites with and without MetS. We assessed age, race and poverty status associated DNAm among AAs (n = 225) and White (n = 233) adults using NCEP-ATP III guidelines. Genome-wide DNAm measurement was assessed using Illumina Infinium Methylation EPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were identified using dmpFinder and bumphunter. EWAS was performed using CpGassoc. We found significant DMPs associated with age, poverty status and MetS in each race. GSTT1(Glutathione S-Transferase Theta 1) was one of the top-hypermethylated genes and MIPEP (Mitochondrial Intermediate Peptidase) was one of the most hypomethylated genes when comparing AAs with and without MetS. PPP1R13L (Protein Phosphatase 1 Regulatory Subunit 13 Like) was the top hypermethylated and SCD (stearoyl-CoA desaturase-1) was one of the most hypomethylated genes for Whites with and without MetS. EWAS results showed that DNAm differences might contribute to MetS risk among Whites and AAs since different genes were identified in AAs and Whites. We replicated previously identified MetS associated genes and found that Thioredoxin-interacting protein (TXN1P) was statistically significantly differentially expressed only in Whites. Our results may be useful in further studies of genes underlying differences in MetS among AAs and Whites.

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

“…Our EWAS revealed 161 replicated associations between 16 CpG sites in eleven loci and 57 unique metabolic measures. All of the eleven epigenetic loci have been previously found to be associated with metabolic traits and processes, primarily based on clinical and biochemical measurements of composite blood lipids [ 14 – 20 , 22 – 25 , 29 , 37 , 38 , 42 , 43 ]. Here, we uncover novel findings with regard to specific features of lipoprotein subclasses such as the lipid compositions and concentrations of each type of lipid in lipoproteins, giving deeper insights into the underlying biology of previous associations.…”

Epigenetics, microRNA and Metabolic Syndrome: A Comprehensive Review

“…The association between aberrant DNA methylation and disease state has been studied across various disorders, including CVDs, autoimmune disorders and various cancers [ 22 , 23 ]. In recent years, epigenome-wide association studies (EWASs) have identified global and locus-specific epigenetic changes potentially involved in the pathophysiological mechanisms responsible for the development of MetS ( Table 1 ) [ 24 , 25 ]. For example, an EWAS study performed in individuals with MetS demonstrated decreased methylation of CPT1A, a gene with a key role in regulating mitochondrial fatty acid oxidation (FAO), to be correlated with the increased metabolic risk and overall MetS phenotype [ 25 ].…”

“…In recent years, epigenome-wide association studies (EWASs) have identified global and locus-specific epigenetic changes potentially involved in the pathophysiological mechanisms responsible for the development of MetS ( Table 1 ) [ 24 , 25 ]. For example, an EWAS study performed in individuals with MetS demonstrated decreased methylation of CPT1A, a gene with a key role in regulating mitochondrial fatty acid oxidation (FAO), to be correlated with the increased metabolic risk and overall MetS phenotype [ 25 ]. In a recent EWAS study in African American adults, MetS was consistently associated with increased methylation in the ABCG1, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signalling and lipid transport [ 24 , 26 ].…”

“…In a recent EWAS study in African American adults, MetS was consistently associated with increased methylation in the ABCG1, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signalling and lipid transport [ 24 , 26 ]. Additionally, it has been shown that marked differences exist in the prevalence of MetS and that of the DNA methylation patterns among middle-aged African Americans and white individuals diagnosed with MetS [ 25 ].…”

Leveraging the Urban–Rural Divide for Epigenetic Research

“…Genetics and environmental exposures both influence phenotype, partly through epigenetic modifications. Genetic architecture affects DNAm in terms of the availability of cytosine-phosphate-guanine (CpG) sites, the efficacy of methylation-related enzyme expression [8,11], how DNAm responds to exposure [12] and inherent NCD risk [2]. Environmental exposures can be either external (behavioral or lifestyle-related factors such as diet, exercise and air purity) or internal (metabolic and biochemical factors such as inflammation and adiposity).…”