Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus.
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 ~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.


CONCLUSIONS
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.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. kamboh@pitt.edu
F Yesim K
FY
Demirci
Amy S
AS
Dressen
Candace M
CM
Kammerer
M Michael
MM
Barmada
Amy H
AH
Kao
Rosalind
R
Ramsey-Goldman
Susan
S
Manzi
M Ilyas
MI
Kamboh
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D050197:Atherosclerosis / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology; D044465:White People / Q000235:genetics
D011516:Prothrombin
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