P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome.
OBJECTIVE
Antiphospholipid antibodies (aPLA) have been shown to enhance thrombus formation by increasing the expression of adhesive receptors such as P-selectin on endothelial cells. The P-selectin counter-receptor on leucocytes is P-selectin glycoprotein ligand-1 (PSGL-1). We have previously described a variable number of tandem repeats (VNTR) polymorphism in the mucin-like region of PSGL-1, with three alleles: allele A, 16 repeats; allele B, 15 repeats; and allele C, 14 repeats.


METHODS
We compared the PSGL-1 VNTR allele and genotype frequencies in 90 patients with antiphospholipid syndrome (APS) with thrombosis, 39 patients with persistent aPLA positivity without thrombosis, and 203 healthy controls.


RESULTS
The frequency of the B allele was significantly higher in patients with APS with thrombosis compared with patients without thrombosis (p = 0.023). When we compared the groups by genotype frequencies, we found a markedly higher frequency of the AB genotype in patients with APS with thrombosis than in aPLA-positive patients without thrombosis (38.9% vs 10.3%, p = 0.001) or in normal population (38.9% vs 22.2%, p<0.01).


CONCLUSIONS
We suggest that the VNTR polymorphism of PSGL-1 is a significant determinant of thrombotic predisposition in patients with APS. Furthermore, risk appears to correlate best with the combination of alleles inherited rather than with the presence of any particular allele.
Diz-Kucukkaya
Reyhan
R
Division of Hematology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. rkucukkaya@hotmail.com
Inanc
Murat
M
Afshar-Kharghan
Vahid
V
Zhang
Q Ed
QE
López
José A
JA
Pekcelen
Yuksel
Y
D000293:Adolescent; D000328:Adult; D016736:Antiphospholipid Syndrome / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013927:Thrombosis / Q000235:genetics*
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein