FLT-1 gene polymorphisms and protein expression profile in rheumatoid arthritis.
OBJECTIVE
Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the FLT-1 polymorphisms with different "angiogenic diseases" suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA.


METHODS
The FLT-1 gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated.


RESULTS
The FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D' = 0.97 and r2 = 0.83. The FLT-1 rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls.


CONCLUSIONS
FLT-1 rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.
Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Agnieszka
A
Paradowska-Gorycka
Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland.
Anna
A
Sowinska
Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
Andrzej
A
Pawlik
Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland.
Damian
D
Malinowski
Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Barbara
B
Stypinska
Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Ewa
E
Haladyj
Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.|Department of Pathophysiology, Warsaw Medical University, Warsaw, Poland.
Katarzyna
K
Romanowska-Prochnicka
Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Marzena
M
Olesinska
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications / Q000235:genetics; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
D015415:Biomarkers; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1