HDL-Associated Paraoxonase 1 as a Bridge between Postmenopausal Osteoporosis and Cardiovascular Disease

Eren, Esin; Elli̇dağ, Hamit Yaşar; Aydın, Özgür; Yılmaz, Necat

doi:10.4068/cmj.2014.50.3.75

Cited by 9 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study found a direct association between the CpG methylation at this locus and HDL-cholesterol levels; other recent studies found an association with diabetes (17,18). The complex interrelations between lipids, diabetes and arterial calcifications merit additional studies (19)(20)(21)(22), our data suggest that the low methylation level at this locus could be associated with higher PHOSPHO1 levels. This could induce calcification due to low HDL cholesterol levels and altered glucose homeostasis or other potential mechanisms.…”

Section: Discussionsupporting

confidence: 67%

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study

Sayols-Baixeras

Subirana

Lluís-Ganella

et al. 2016

Human Molecular Genetics

View full text Add to dashboard Cite

Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2,542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was inversely associated with methylation of their corresponding CpGs (P-value = 0.0042 and 0.0045, respectively) in participants of the GOLDN study (n = 98). In turn, SREBF1 expression was directly associated with HDL cholesterol (P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism.

show abstract

Section: Discussionsupporting

confidence: 67%

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study

Sayols-Baixeras

Subirana

Lluís-Ganella

et al. 2016

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…The pathophysiology of HHcy-derived CVD in RA patients is largely uncharacterized. Nevertheless, indirect evidence from relevant observations in the general population together with the crucial role of inflammation push forward our understanding of the several derangements that may interact to cause or exacerbate it [ 6 , 11 , 12 , 14 , 21 , 22 , 36 – 38 , 44 – 51 ]. They include: i) oxidative stress [ 12 , 44 ] ii) chronic inflammation and immune activation [ 11 , 14 , 37 , 38 , 45 ] iii) propensity for a pro-atherogenic lipid profile [ 44 – 47 ] iv) poor disease status and severe radiological damage [ 6 , 12 , 38 , 44 ] v) thrombophilia [ 21 , 22 , 38 ] vi) increase of plasma ADMA levels [ 14 , 48 ] vii) osteoprotegerin [ 49 ] viii) genetic and epigenetic factors [ 36 , 50 , 51 ].…”

Section: Association Between Hyperhomocysteinemia and Cardiovascular mentioning

confidence: 99%

Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients

Essouma¹,

Noubiap

2015

Biomark Res

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population. Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved. Hence, anti-inflammatory strategies such as homocysteine-lowering interventions are warranted. Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs. Most importantly in the pathophysiology of hyperhomocysteinemia and its related cardiovascular diseases in RA, there is a bi-directional link between immuno-inflammatory activation and hyperhomocysteinemia. As such, chronic immune activation causes B vitamins (including folic acid) depletion and subsequent hyperhomocysteinemia. In turn, hyperhomocysteinemia may perpetrate immuno-inflammatory stimulation via nuclear factor ƙappa B enhancement. This chronic immune activation is a key determinant of hyperhomocysteinemia-related cardiovascular diseases in RA patients. Folate, a homocysteine-lowering therapy could prove valuable for cardiovascular disease prevention in RA patients in the near future with respect to homocysteine reduction along with blockade of subsequent oxidative stress, lipid peroxidation, and endothelial dysfunction. Thus, large scale and long term homocysteine-lowering clinical trials would be helpful to clarify the association between hyperhomocysteinemia and cardiovascular diseases in RA patients and to definitely state conditions surrounding folic acid supplementation. This article reviews direct and indirect evidence for cardiovascular disease prevention with folic acid supplementation in RA patients.

show abstract

“…Furthermore, visceral obesity as a hallmark of MetS is associated with increased levels of adiponectin and reduced production of leptin, which could also contribute to loss of bone mass [19,20]. Low HDL levels, high TG levels and elevated blood pressure are associated with the development of arteriosclerosis and have been suggested to promote the loss of BMD, as small arteries, which provide blood supply for bone metabolism, are affected [21,22,23,24,25]. …”

Section: Introductionmentioning

confidence: 99%

Association between Metabolic Syndrome and Bone Mineral Density - Data from the Berlin Aging Study II (BASE-II)

Eckstein¹,

Buchmann²,

Demuth³

et al. 2016

Gerontology

View full text Add to dashboard Cite

Background: Decreased bone mineral density (BMD) has been linked to metabolic disorders, such as type 2 diabetes. However, results regarding the metabolic syndrome (MetS), a cluster of at least 3 of 5 cardiovascular risk parameters with potentially contradictory effects on BMD are still inconclusive. Objective: We investigated the effect of MetS and its single parameters on BMD at 3 sites in community-dwelling older subjects. Methods: 1,402 subjects (51.1% female, 68 ± 4 years old) from the Berlin Aging Study II (BASE-II) were included. MetS was defined as suggested by IDF/NHLBI/AHA. Insulin resistance (IR) was assessed by the homeostasis model of IR. BMD (lumbar spine, femur neck, hip) and trunk fat were measured by dual-energy X-ray absorptiometry. Osteoporosis was defined by a T score of ≤-2.5. Results: MetS was present in 29.6% of women and 41.7% of men. In regression models, we observed a positive association of MetS with the BMD of the lumbar spine (p = 0.005) and hip (p = 0.028) in women even after adjustment for risk factors, but no effect of the single parameters apart from IR. In contrast, there was no association between MetS and BMD in men. However, higher trunk fat and higher waist circumference were associated with lower levels of BMD in men with or without MetS (p < 0.05). Conclusion: We obtained different results in men and women. In women, the positive though slight effect of MetS on BMD could not be explained by single MetS components apart from IR. In men, central obesity was negatively associated with BMD, suggesting that the metabolic effects driven by visceral fat have a negative impact.

show abstract

HDL-Associated Paraoxonase 1 as a Bridge between Postmenopausal Osteoporosis and Cardiovascular Disease

Cited by 9 publications

References 38 publications

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study

Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients

Association between Metabolic Syndrome and Bone Mineral Density - Data from the Berlin Aging Study II (BASE-II)

Contact Info

Product

Resources

About