Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

Abstract

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.

<b><i>NT5C2</i></b> Gene Polymorphisms and the Risk of Coronary Heart Disease

“…It has been proposed that NT5C2 regulates the intracellular concentration of inosine 5′-monophosphate and guanosine 5′-monophosphate and the production of UA [14]. NT5C2 also has potential therapeutic importance since it can phosphorylate some anti-tumor and antiviral nucleoside analogs [14, 20, 30]. A previous study implied that NT5C2 influences a reduction in both visceral and subcutaneous fat mass, which relates to CVD morbidity and mortality [31].…”

“…However, most of these reports were obtained from genome-wide association studies (GWAS) and are not supported by detailed studies. Importantly, few studies have focused on the relationship between NT5C2 polymorphisms and CHD risk [19, 20].…”

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

“…Importantly, elevated TGF-β1 levels and altered downstream signalling have been implicated in the etiology of atherosclerosis 26 , vessel restenosis 27 and in the development of the neointima 28 . Genome-wide association studies have also identified chromosome 14q32 as a locus for a hitherto uncharacterized gene called HHIPL1 (Hedgehog interacting protein-like 1) 29 which encodes a sequence homolog of an antagonist of hedgehog signalling that is secreted as a pro-atherogenic protein to regulate lesion formation 30 .…”

Genetics of Non-Alcoholic Fatty Liver and Cardiovascular Disease: Implications for Therapy?

“…PEMT rs12936587 variant was associated with increased susceptibility to CAD (OR 1.07, 95% CI 1.05-1.09, p = 4.45x10 −10 ) (Schunkert et al, 2011) in a meta-analysis of 14 GWAS (22,233 cases of CAD and 64,762 controls). However, there was no association with cardiovascular events (IHD, CVA, peripheral arterial disease), and atherosclerosis determined by carotid intima-media wall thickness (IMT) by carotid ultrasonography in a detailed study of 2,609 Spanish individuals (López-Mejías et al, 2017).…”