Relationship between two sequence variations in the gene for peroxisome proliferator-activated receptor-gamma and plasma homocysteine concentration. Health in men study

Golledge, Jonathan; Norman, Paul

doi:10.1007/s00439-007-0446-8

Cited by 10 publications

(16 citation statements)

References 32 publications

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“…AAA was defined as maximum infrarenal aortic diameter ≥30mm. The definitions of clinical risk factors such as hypertension, dyslipidaemia, and CHD were as previously described [7]. …”

Section: Methodsmentioning

confidence: 99%

Association of an allele on chromosome 9 and abdominal aortic aneurysm

et al. 2010

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Objective Abdominal aortic aneurysm (AAA) has been recognized as a multi-factorial disease with both genetic and environmental risk factors. A locus residing within non-coding DNA on chromosome 9p21.3 has recently been associated with AAA. To further investigate the significance of this site for AAA, we performed an association study on a large group of 3,371 men aged 65-83 years of whom 513 had an AAA. Methods All men were assessed for other risk factors in a uniform way and an ultrasound of the abdominal aorta was performed. Results Our findings validated the strong association of the chromosome 9p21.3 SNPs rs10757278 and rs1333049 with AAA and demonstrated the upregulation of LINE-1 elements at the site of AAA. Conclusion This study confirms a reproducible association between risk alleles on chromosome 9p21.3 and AAA. We also provide preliminary evidence for an association of LINE-1 elements with AAA which will require further investigation.

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“…AAA was defined as maximum infrarenal aortic diameter ≥30mm. The definitions of clinical risk factors such as hypertension, dyslipidaemia, and CHD were as previously described [7]. …”

Section: Methodsmentioning

confidence: 99%

Association of an allele on chromosome 9 and abdominal aortic aneurysm

et al. 2010

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“…The Health in Men Study is a study of men aged ≥65 years who originally participated in a population‐based randomized controlled trial of screening for AAA. Details of the design of these studies, including definitions of clinical risk factors, have been reported previously 15–17 …”

Section: Methodsmentioning

confidence: 99%

Association of PPARγ allelic variation, osteoprotegerin and abdominal aortic aneurysm

Moran

Clancy

Biroš

et al. 2009

Clinical Endocrinology

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Objective-We have previously demonstrated high concentrations of the glycoprotein osteoprotegerin (OPG) in biopsies of abdominal aortic aneurysm (AAA) and demonstrated that ligation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) downregulates OPG in vitro and within a mouse model. The aims of this study were to assess the associations between circulating concentrations of OPG, polymorphisms of the gene encoding PPARγ (PPARG), AAA presence and growth.Design, patients and measurements-Two genetic polymorphisms in PPARG were assessed in 4227 men, 699 of whom had an AAA. For 631 men, who had AAAs, maximum aortic diameter was monitored by yearly ultrasound for a median of 5 years. Plasma OPG was measured in 838 men, 318 of whom had an AAA.Results-Plasma concentrations of OPG were independently associated with AAA (adjusted odds ratio 1.38, 95% CI 1.10-1.72). The PPARG c.1347C>T polymorphism was associated with plasma concentrations of OPG (beta 0.12, p<0.01). The PPARG c.34G>C polymorphism was weakly associated with AAA (adjusted odds ratio 1.28, 95% CI 1.01-1.61). PPARG c.1347C>T was associated with increased AAA growth (recessive model, p=0.03).Conclusions-Circulating concentrations of OPG are associated with AAA and with one PPARG polymorphism. PPARG polymorphisms are weakly associated with AAA presence and growth. Confirmation of these findings is required in other cohorts.

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“…For example, sequence variation of methylenetetrahydrofolate reductase (MTHFR) gene has been shown to influence circulating homocysteine level [83], and sequence variation of amino acid 222 from alanine to valine (p.A222V) has been reported to elevate circulating concentrations of homocysteine [84]. The PPAR γ produces a number of isoforms which control a variety of pathways including lipid metabolism, insulin sensitivity, and inflammation [85].…”

Section: Homocysteine Protein Modification and Hypertension: Thementioning

confidence: 99%

Homocysteine and Hypertension in Diabetes: Does PPARγHave a Regulatory Role?

Sen

Tyagi

2010

PPAR Research

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Dysfunction of macro- and microvessels is a major cause of morbidity and mortality in patients with cardio-renovascular diseases such as atherosclerosis, hypertension, and diabetes. Renal failure and impairment of renal function due to vasoconstriction of the glomerular arteriole in diabetic nephropathy leads to renal volume retention and increase in plasma homocysteine level. Homocysteine, which is a nonprotein amino acid, at elevated levels is an independent cardio-renovascular risk factor. Homocysteine induces oxidative injury of vascular endothelial cells, involved in matrix remodeling through modulation of the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) axis, and increased formation and accumulation of extracellular matrix protein, such as collagen. In heart this leads to increased endothelial-myocyte uncoupling resulting in diastolic dysfunction and hypertension. In the kidney, increased matrix accumulation in the glomerulus causes glomerulosclerosis resulting in hypofiltration, increased renal volume retention, and hypertension. PPARγ agonist reduces tissue homocysteine levels and is reported to ameliorate homocysteine-induced deleterious vascular effects in diabetes. This review, in light of current information, focuses on the beneficial effects of PPARγ agonist in homocysteine-associated hypertension and vascular remodeling in diabetes.

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Relationship between two sequence variations in the gene for peroxisome proliferator-activated receptor-gamma and plasma homocysteine concentration. Health in men study

Cited by 10 publications

References 32 publications

Association of an allele on chromosome 9 and abdominal aortic aneurysm

Association of an allele on chromosome 9 and abdominal aortic aneurysm

Association of PPARγ allelic variation, osteoprotegerin and abdominal aortic aneurysm

Homocysteine and Hypertension in Diabetes: Does PPARγHave a Regulatory Role?

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