Also, a recent study has supported the use of carotid US in the a

Also, a recent study has supported the use of carotid US in the assessment of the CV risk of RA patients. A large scale study has disclosed several loci associ ated with CAD. Interestingly, in this study both the ZC3HC1 rs11556924 polymorphism was associated with CAD in non rheumatic Caucasian individuals. There fore, in spite of having a moderate effect on CAD as com pared to other genetic variants described by Schunkert Inhibitors,Modulators,Libraries et al, such as polymorphisms in CDKN2A, SORT1, LDLR, MRPS6 and MIA3, we assessed this time the ZC3HC1 rs11556924 polymorphism because we had already ana lyzed the potential role of some others. In this regard, we previously showed that the rs599839 polymorphism lo cated in the lp13. 3 genomic region was associ ated with endothelial dysfunction Inhibitors,Modulators,Libraries in RA.

In addition, we reported an association between MIA3 rs17465637 A allele Inhibitors,Modulators,Libraries with Inhibitors,Modulators,Libraries the risk of CV events in RA patients with dyslipidemia. The assessment of the potential influ ence of other polymorphisms in the risk of CV disease in RA, such as CDKN2A and CDKN2B, LDLR, MRPS6, PPAP2B and ADAMST7, among others, is still underway. ZC3HC1, also called NIPA, is a mammalian F box like protein that monitors the tim ing of mitotic entry and in complex with constitutively ac tive oncogenic proteins contributes to the development of carcinogenesis. Since it has been shown that media tors of angiogenesis may play an important role in the regulation of endothelial integrity and inflammation, it is possible that changes in the stability and functional properties of ZC3HC1 protein may play a role in the endothelial dysfunction and, in the long run, in the devel opment of atherosclerosis.

Since the incidence of CV disease is increased in pa tients with RA, we assessed for the first time the poten tial association between this polymorphism and subclinical atherosclerosis in RA. Our results show that RA patients carrying the TT geno type have significantly higher cIMT values than those RA patients carrying the CC genotype, even after adjusting for potential Inhibitors,Modulators,Libraries confounders, supporting the evidence that the genetic component plays a relevant role in the develop ment of CV disease in RA. These results showing an association with the TT genotype apparently seem to be in contradiction with the data described by Schunkert et al. that reported an association of the C allele with the risk of CAD.

However, it is important to highlight that the populations analyzed in our study and in the study by Schunkert et al. are different. In this regard, Schunkert et al. performed their study in non rheumatic Caucasian definitely individuals while we assessed Spanish RA patients with a chronic inflammatory disease. Therefore, while in patients with RA the presence of a chronic inflammatory burden may lead to accelerated atheroscler osis, it may not be the case for the development of athero sclerosis in healthy individuals.

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