Genetic variants of TNFSF4 and risk for carotid artery disease and stroke

Olofsson, Peder S.; Söderström, Lars; Jern, Christina; Sirsjö, Allan; Ria, Massimiliano; Sundler, E.; Fairé, Ulf dé; Wiklund, Peder; Öhrvik, John; Hedin, Ulf; Paulsson-Berne, Gabrielle; Hamsten, Anders; Eriksson, Per; Hansson, Göran K.

doi:10.1007/s00109-008-0412-5

Cited by 36 publications

(30 citation statements)

References 292 publications

(455 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…these results were consistent with those of Koch et al who did not find any association between the TNFSF4 gene and mi in a German population (13). in addition, Olofsson et al, in an association study of TNFSF4 gene variations with the risk for ischemic stroke using expression analysis, no significant association was found (14).…”

Section: Discussionsupporting

confidence: 92%

Lack of evidence to support the association of polymorphisms within the TNFSF4 gene and coronary heart disease in a Chinese Han population

Cheng¹,

Wang²,

Chen³

et al. 2010

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. coronary heart disease (chd) is a complex disorder resulting from the interaction of a number of genetic and environmental factors. increasing evidence has shown that Ox40 ligand (Ox40l), also known as tumor necrosis factor superfamily member 4 (tnFSF4), plays a key role in the pathogenesis of atherosclerosis. however, there have been inconsistent reports in various populations, and further studies are required to clarify this issue. a gene-based association study was conducted using five single-nucleotide polymorphisms (SNPs) reported in previous studies. The five SNPs (rs1234314, rs45454293, rs3850641, rs1234313 and rs3861950) were genotyped in 547 unrelated chd patients and 601 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism. rs1234314, rs3850641 and rs3861950 were further genotyped in an additional 512 cases and 520 controls using the taqman Snp genotyping method. a possible relationship between the five SNPs and the severity of CHD was investigated. The results revealed no significant association between the TNFSF4 polymorphism and chd. in addition, the stratified analysis of genotypic and allelic frequencies showed no association between the TNFSF4 polymorphism and chd in either gender. Finally, no significant correlation between the TNFSF4 polymorphism and chd severity was detected. These findings do not support a role of the TNFSF4 gene in chd pathogenesis in the chinese han population. Introductioncoronary heart disease (chd) is the leading cause of death in industrialized countries, and its prevalence is rapidly increasing in China. Recent research has shown that inflammation plays a critical role in chd pathogenesis and in other manifestations of atherosclerosis (1). Experimental evidence has confirmed that activated T cells are implicated in atherogenesis (2,3).numerous studies have implicated tnFSF4/tnFrSF4 in the activation of t cells, as well as that of macrophages (4). TNFSF4, also known as Ox40l, is primarily expressed by activated B cells, vessel endothelial cells, macrophages, dendritic cells and certain activated t cells. this generates costimulatory signals by interacting with tnFrSF4 on activated t lymphocytes and enhances the proliferation and differentiation of t lymphocytes and the development and survival of memory t cells (5). thus, it is suggested that the tnFSF4-tnFrSF4 pathway plays a key role in atherosclerosis through its participation in t cell activation. numerous genetic studies have indicated a relationship between tnFSF4-tnFrSF4 and cardiovascular diseases. in 2006, ria et al confirmed that genetic variation in TNFRSF4 was associated with myocardial infarction (mi) in a Swedish population (6). Furthermore, mashimo et al found an association between TNFRSF4 gene polymorphisms and essential hypertension (7). there is current evidence showing that TNFSF4 is the gene underlying the atherosclerosis susceptibility locus 1 (ath1) in mice, and that genetic polymorphisms in TNFSF4 are associated with mi an...

show abstract

Section: Discussionsupporting

confidence: 92%

Lack of evidence to support the association of polymorphisms within the TNFSF4 gene and coronary heart disease in a Chinese Han population

Cheng¹,

Wang²,

Chen³

et al. 2010

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Fifteen patients scheduled for carotid endarterectomy were included (31). Nine atherosclerotic lesions were snap-frozen.…”

Section: Human Biopsiesmentioning

confidence: 99%

“…Sections were rinsed, incubated with ImmPress (Vector, Burlingame, CA, USA) for 30 min, followed by Nova Red substrate (Vector), and counterstained with Hematoxylin QS (Vector). Samples from the Biobank of Karolinska Carotid Endarterectomies (BiKE) were obtained and analyzed using global transcript analysis with Affymetrix ® gene arrays as previously described (31,32).…”

Section: Human Biopsiesmentioning

confidence: 99%

See 1 more Smart Citation

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

Krivospitskaya

Elmabsout

Sundman

et al. 2012

Mol Med

View full text Add to dashboard Cite

All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26) enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic arteries than in normal arteries. Databases were queried for nonsynonymous CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophagelike cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions, as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.

show abstract

“…OX40L deficiency renders mice less susceptible to atherosclerosis, whereas OX40L overexpression enhances the development of atherosclerosis (17). In humans, SNPs in both the OX40 and OX40L genes affect the incidence of cardiovascular disease (17,19,20).…”

mentioning

confidence: 99%

Interruption of the OX40–OX40 Ligand Pathway in LDL Receptor–Deficient Mice Causes Regression of Atherosclerosis

Foks

Puijvelde

Bot

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Patients suffering from cardiovascular disease have well-established atherosclerotic lesions, rendering lesion regression of therapeutic interest. The OX40 (TNFRSF4)–OX40 ligand (OX40L; TNFSF4) pathway is important for the proliferation and survival of T cells, stimulates B cells, and is associated with cardiovascular disease. We hypothesized that interference with the OX40–OX40L pathway, in combination with decreases in cholesterol, may induce regression of atherosclerosis. LDLr−/− mice were fed a Western-type diet for 10 wk, after which they received chow diet and were treated with anti-OX40L or PBS for 10 wk. A significant regression of lesions was observed in the aorta and aortic arch of anti-OX40L–treated mice compared with control mice. Interference of the OX40–OX40L pathway reduced Th2 responses, as shown by decreases in GATA-3 and IL-4 levels. Also, IgE levels were decreased, as demonstrated by reduced mast cell presence and activation. Notably, IL-5 production by T and B1 cells was increased, thus enhancing atheroprotective oxidized low-density lipoprotein–specific IgM production. The increase in IL-5 production and IgM was mediated by IL-33 production by APCs upon OX40L blockade. We conclude that interruption of the OX40–OX40L signaling pathway, combined with decreases in dietary cholesterol, induces the regression of atherosclerosis through induction of IL-5–producing T cells and oxidized low-density lipoprotein–specific IgM and reductions in Th2 and mast cells.

show abstract

Genetic variants of TNFSF4 and risk for carotid artery disease and stroke

Cited by 36 publications

References 292 publications

Lack of evidence to support the association of polymorphisms within the TNFSF4 gene and coronary heart disease in a Chinese Han population

Lack of evidence to support the association of polymorphisms within the TNFSF4 gene and coronary heart disease in a Chinese Han population

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

Interruption of the OX40–OX40 Ligand Pathway in LDL Receptor–Deficient Mice Causes Regression of Atherosclerosis

Contact Info

Product

Resources

About