F9 Malmö, factor IX and deep vein thrombosis.
BACKGROUND
We recently reported the association between the Malmö sequence variant in F9 (rs6048) and deep vein thrombosis.


METHODS
We aimed to study whether the association between F9 Malmö and deep vein thrombosis is explained by linkage disequilibrium with nearby single-nucleotide polymorphisms, and whether the association is explained biologically by F9 Malmö affecting factor IX antigen levels or activation of factor IX. We investigated the association of F9 Malmö and 28 nearby single-nucleotide polymorphisms with deep vein thrombosis in men from two case-control studies, LETS (n=380) and MEGA (n=1,469). We assessed the association of F9 Malmö with factor IX antigen level in male control subjects from LETS (n=191) and two subsets of MEGA (n=823 and n=484) and the association with endogenous thrombin potential in LETS control men. We studied the association between F9 Malmö and factor IX activation peptide in 1,199 healthy middle-aged men from the NPHS-II cohort.


RESULTS
In the combined LETS and MEGA studies, the odds ratio (95% confidence interval) for the G allele of F9 Malmö, compared with the A allele, was 0.80 (0.69-0.93). One single-nucleotide polymorphism in F9, rs422187, was strongly linked to F9 Malmö (r(2)=0.94) and was similarly associated with deep vein thrombosis. No other single-nucleotide polymorphism or haplotype tested was more strongly associated. Factor IX antigen level, factor IX activation peptide levels and endogenous thrombin potential did not differ between F9 Malmö genotypes.


CONCLUSIONS
The F9 Malmö sequence variant was the most strongly associated with deep vein thrombosis among common single-nucleotide polymorphisms in the region. However, the biological mechanism by which F9 Malmö affects risk remains unknown.
Bezemer
Irene D
ID
Department of Clinical Epidemiology, C7-P Leiden University Medical Center, Leiden, The Netherlands.
Arellano
Andre R
AR
Tong
Carmen H
CH
Rowland
Charles M
CM
Ireland
Helen A
HA
Bauer
Kenneth A
KA
Catanese
Joseph
J
Reitsma
Pieter H
PH
Doggen
Carine J M
CJ
Devlin
James J
JJ
Rosendaal
Frits R
FR
Bare
Lance A
LA
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D041321:Chromosomes, Human, X / Q000235:genetics; D005164:Factor IX / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics*; D055815:Young Adult
D005164:Factor IX