Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis

Abstract

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA.

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

“…The NLRP3 rs4612666 gene polymorphism may affect the risk of having a large artery atherosclerosis-induced ischemic stroke 47 . However, NLRP3 rs12239046 allele was not associated with cardiovascular disease 48 . Fewer studies have examined the association of the NLRP3 genotypes with cancer.…”

Mechanisms of vascular comorbidity in autoimmune diseases

“…It was assessed whether they were of influence on the development of CVEs and subclinical atherosclerosis in this special clinical subgroup. Interestingly, no association could be shown between these genes and CVEs in rheumatoid arthritis [ 14 ].…”

Biology of IL‐38 and its role in disease

“…A more recent study investigated the association of this IL‐38 polymorphism (and the other CRP‐level associated polymorphisms) with cardiovascular disease in a group of patients with rheumatoid arthritis, but did not identify an association . Another GWAS study including 425 non‐diabetic individuals from West Africa showed that 10 polymorphisms in the genes of the IL‐1 family, including one in IL‐38, were associated with high plasma IL‐1Ra concentrations .…”

“…30 A more recent study investigated the association of this IL-38 polymorphism (and the other CRP-level associated polymorphisms) with cardiovascular disease in a group of patients with rheumatoid arthritis, but did not identify an association. 31 Another GWAS study including 425 non-diabetic individuals from West Africa showed that 10 polymorphisms in the genes of the IL-1 family, including one in IL-38, were associated with high plasma IL-1Ra concentrations. 32 It has also been demonstrated that the IL-38 polymorphism (rs3811058), is significantly differentially distributed in a Mexican population when compared to Caucasian, Asian, and African populations.…”