Journal article
Functional Polymorphisms of the Coagulation Factor II Gene (F2) and Susceptibility to Systemic Lupus Erythematosus
Journal of rheumatology, v 38(4), pp 652-657
01 Apr 2011
PMID: 21239755
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objective. Two F2 functional polymorphisms, rs1799963 (G20210A) and rs3136516 (A19911G), are known to be associated with elevated levels/activity of prothrombin (encoded by F2) and risk of thrombosis. Since patients with systemic lupus erythematosus (SLE) have high risk of thrombosis and accelerated atherosclerosis and also high prevalence of anti-prothrombin antibodies, we hypothesized that these two F2 polymorphisms could affect risk of SLE.
Methods. We investigated these polymorphisms in 627 women with SLE (84% Caucasian Americans, 16% African Americans) and 657 female controls (78% Caucasian Americans, 22% African Americans).
Results. While the rs1799963 A allele was almost absent in African Americans, it was present at similar to 2% frequency in Caucasian Americans and showed no significant association with SLE. The rs3136516 G allele frequency was significantly higher in Caucasian SLE cases than in controls (48.4% vs 43.7%, respectively) with a covariate-adjusted odds ratio (OR) of 1.22 (95% CI 1.03-1.46, p = 0.023). The association was replicated in African Americans (rs3136516 G allele frequency 91.2% in cases vs 82.2% in controls) with an adjusted OR of 1.96 (95% CI 1.08-3.58, p = 0.022). Stratification of Caucasian SLE patients based on the presence or absence of cardiac and vascular events (CVE) revealed stronger association with the CVE-positive SLE subgroup than the CVE-negative SLE subgroup (OR 1.42 vs 1.20). Prothrombin activity measurements in a subset of SLE cases demonstrated higher activity in the carriers of the rs3136516 G allele.
Conclusion. Our results suggest a potential role for prothrombin and the crosstalk between hemostatic and immune/inflammatory systems in SLE and SLE-associated cardiovascular events, which warrants further investigation in independent samples. (First Release Jan 15 2011; J Rheumatol 2011;38:652-7; doi:10.3899/jrheum.100728)
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Details
- Title
- Functional Polymorphisms of the Coagulation Factor II Gene (F2) and Susceptibility to Systemic Lupus Erythematosus
- Creators
- F. Yesim K. Demirci - University of PittsburghAmy S. Dressen - University of PittsburghCandace M. Kammerer - University of PittsburghM. Michael Barmada - University of PittsburghAmy H. Kao - University of PittsburghRosalind Ramsey-Goldman - Center for RheumatologySusan Manzi - University of PittsburghM. Ilyas Kamboh - University of Pittsburgh
- Publication Details
- Journal of rheumatology, v 38(4), pp 652-657
- Publisher
- J Rheumatol Publ Co
- Number of pages
- 6
- Grant note
- R01-HL088648; R01-AR057028; R01-AR046588; K24-AR002213; K24-AR002138; P60-AR48098 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA UL1RR024153 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R01HL088648 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01AR057028 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) UL1TR000005 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000289333800012
- Scopus ID
- 2-s2.0-79953294312
- Other Identifier
- 991021933905704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Rheumatology