In:
Arthritis & Rheumatology, Wiley, Vol. 71, No. 3 ( 2019-03), p. 351-360
Abstract:
To investigate the genetic background influencing the development of cardiovascular ( CV ) disease in patients with rheumatoid arthritis ( RA ). Methods We performed a genome‐wide association study ( GWAS ) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima‐media thickness ( CIMT ) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals. Results A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome‐wide level of significance (minor allele [G] β coefficient 0.142, P = 1.86 × 10 −8 ). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein–protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate–adjusted P = 4.01 × 10 −3 ). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB 1 , MSRA , and ZC 3 HC 1 ( P = 8.12 × 10 −4 , P = 5.94 × 10 −4 , and P = 2.46 × 10 −4 , respectively). Conclusion The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA .
Type of Medium:
Online Resource
ISSN:
2326-5191
,
2326-5205
DOI:
10.1002/art.2019.71.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2754614-7