GSTM1 polymorphism in patients with clinical manifestations of atherosclerosis

Rodrigues, D.A.; Martins, J.V.M.; Silva, K.S.F. e; Costa, Iasmim Ribeiro da; Lagares, M.H.; Campedelli, Fábio Lemos; Barbosa, A.M.; Morais, Mariana Patrício de; Moura, K.K.V.O.

doi:10.4238/gmr16019101

Cited by 11 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A study in north India found no significant difference in any lipid phenotype between individuals with GSTM1 (-) and GSTM1 (+), but did find that the GSTM1 (-) genotype had a 2-fold increased risk of developing coronary artery disease in the cohort [60]. This gene has also been studied for association with atherosclerosis, and frequency of atherosclerosis in a GSTM1 polymorphic group were found to be 1.2 times higher than those in the control group in a study from a Brazilian cohort [61].…”

Section: Discussionmentioning

confidence: 99%

Genetically regulated gene expression underlies lipid traits in Hispanic cohorts

2019

View full text Add to dashboard Cite

Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted in genetic variation underlying lipid levels, they mainly comprise individuals of European ancestry and thus their transferability to non-European populations is unclear. We performed genome-wide (GWAS) and imputed transcriptome-wide association studies of four lipid traits in the Hispanic Community Health Study/Study of Latinos cohort (HCHS/SoL, n = 11,103), replicated top hits in the Multi-Ethnic Study of Atherosclerosis (MESA, n = 3,855), and compared the results to the larger, predominantly European ancestry meta-analysis by the Global Lipids Genetics Consortium (GLGC, n = 196,475). In our GWAS, we found significant SNP associations in regions within or near known lipid genes, but in our admixture mapping analysis, we did not find significant associations between local ancestry and lipid phenotypes. In the imputed transcriptome-wide association study in multiple tissues and in different ethnicities, we found 59 significant gene-tissue-phenotype associations (P < 3.61×10 −8 ) with 14 unique significant genes, many of which occurred across multiple phenotypes, tissues, and ethnicities and replicated in MESA (45/59) and in GLGC (44/59). These include well-studied lipid genes such as SORT1 , CETP , and PSRC1 , as well as genes that have been implicated in cardiovascular phenotypes, such as CCL22 and ICAM1 . The majority (40/59) of significant associations colocalized with expression quantitative trait loci (eQTLs), indicating a possible mechanism of gene regulation in lipid level variation. To fully characterize the genetic architecture of lipid traits in diverse populations, larger studies in non-European ancestry populations are needed.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetically regulated gene expression underlies lipid traits in Hispanic cohorts

2019

View full text Add to dashboard Cite

show abstract

“…Lower GSTM1 CG methylation content leads to the higher GSTM1 mRNA expression in T cells and knockdown of GSTM1 mRNA expression decreases T cells polarization to Th1 differentiation. GSTM1 genetic polymorphisms have been implicated in many diseases including atherosclerosis [ 37 ], and bladder cancer [ 38 ]. We are the first to show epigenetic control of the aging-dependent GSTM1 promoter methylation on suppression of the redox GSTM1 gene expression and lymphocyte T cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation

et al. 2017

View full text Add to dashboard Cite

This study investigated whether aging was associated with epigenetic changes of DNA hypermethylation on immune gene expression and lymphocyte differentiation. We screened CG sites of methylation in blood leukocytes from different age populations, picked up genes with age-related increase of CG methylation content more than 15%, and validated immune related genes with CG hypermethylation involved in lymphocyte differentiation in the aged population. We found that 12 genes (EXHX1、 IL-10、 TSP50、 GSTM1、SLC5A5、SPI1、F2R、LMO2、PTPN6、FGFR2、MMP9、MET) were associated with promoter or exon one DNA hypermethylation in the aged group. Two immune related genes, GSTM1 and LMO2, were chosen to validate its aging-related CG hypermethylation in different leukocytes. We are the first to validate that GSTM1_P266 and LMO2_E128 CG methylation contents in T lymphocytes but not polymorphonuclear cells (PMNs) or mononuclear cells (MNCs) were significantly increased in the aged population. The GSTM1 mRNA expression in T lymphocytes but not PMNs or MNCs was inversely associated with the GSTM1 CG hypermethylation levels in the aged population studied. Further studies showed that lower GSTM1 CG methylation content led to the higher GSTM1 mRNA expression in T cells and knockdown of GSTM1 mRNA expression decreased type 1 T helper cell (Th1) differentiation in Jurkat T cells and normal adult CD4 T cells. The GSTM1_P266 hypermethylation in the aged population associated with lower GSTM1 mRNA expression was involved in Th1 differentiation, highlighting that modulation of aging-associated GSTM1 methylation may be able to enhance T helper cell immunity in the elders.

show abstract

“…They catalyze the reduced form of glutathione into xenobiotic substrates, turning such compounds more water-soluble in order to fulfill their function of detoxification [72]. GSTs polymorphisms are linked to innumerous diseases and anomalies such cancer [73], drug resistance [74], diabetes [75], atherosclerosis [39,40], and other inflammatory [76] and autoimmune diseases [77,78].…”

Section: Glutathione S-transferasementioning

confidence: 99%

“…GSTs from the mu and theta classes are particularly polymorphic. Null mutations in GSTM1 have been associated with a large variety of diseases and an increased susceptibility to toxins [39,73]. Null mutations in GSTM1 increases the susceptibility diseases as well [40,75].…”

Section: Glutathione S-transferasementioning

confidence: 99%

“…Hundreds of genes have been reported to be related to atherosclerosis and they regulated a myriad of physiological processes, including macromolecules metabolism, coagulation, detoxification, endothelial function and coagulation. Several of those genes are polymorphic and variations in their sequence contribute to the molecular pathogenesis of the disease [37][38][39][40][41]. The inherited risk of atherosclerosis is increased in families with multiple affected members [42].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The multifaceted role of genetic polymorphisms in atherosclerosis

Silva¹

2018

Heart Cardiovasc Disord

View full text Add to dashboard Cite

Atherosclerosis is one of the most investigated disorders among cardiovascular anomalies and its clinical manifestations are responsible for the deaths of over 17 million patients worldwide. Atheromatous plaques block the blood flux and bring about long-term serious consequences. Although the precise cause is still unknown, atherosclerosis onset is related to risk factors such as high cholesterol levels, high blood pressure, obesity, diabetes, smoking, imbalanced diet, family history and genetic predisposition. The inherited risk of atherosclerosis is increased in families with multiple affected members. Therefore, family history of atherosclerosis account for genetic counseling and genetic testing. In the present review, we explore the influence of genetic polymorphism of target genes (eNOS, GSTM1, GSTT1 and TP53) and on atherosclerosis. Here we show the possible influence of genetic polymorphisms and atherosclerosis. Knowledge of genetic variants that increase susceptibility of atherosclerosis may launch more efficient methods of prevention, diagnostic, treatment, and genetic counseling in the important field of cardiology. Although discrepancies are seen, each target gene show promisor activity as atherosclerosis markers that could be used in diagnostic and treatment.

show abstract

GSTM1 polymorphism in patients with clinical manifestations of atherosclerosis

Cited by 11 publications

References 20 publications

Genetically regulated gene expression underlies lipid traits in Hispanic cohorts

Genetically regulated gene expression underlies lipid traits in Hispanic cohorts

Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation

The multifaceted role of genetic polymorphisms in atherosclerosis

Contact Info

Product

Resources

About