The impact of platelet membrane glycoprotein Ib alpha and Ia/IIa polymorphisms on the risk of thrombosis in the antiphospholipid syndrome.
BACKGROUND
Pathogenesis of thrombus formation in antiphospholipid syndrome (APS) is not clear. Platelet membrane glycoprotein (GP) receptors play important roles in development of thrombosis.


OBJECTIVE
We investigated the association between development of thrombosis in APS and polymorphisms of GPIb alpha variable number of tandem repeats (VNTR), Kozak, and GPIa C807T. Patients/Methods Sixty patients with APS (30 with proven thrombosis and 30 without thrombosis) and 63 controls were included. Presence of GPIa C807T polymorphism was determined with real-time PCR and GPIb alpha Kozak and VNTR polymorphisms by conventional PCR.


RESULTS
Frequency of C807T TT genotype was significantly higher in APS with thrombosis than APS without thrombosis (p=0.023) and also in APS with multiple thrombi compared to APS without thrombi (p=0.023). Frequency of Kozak TC genotype was higher in APS with arterial thrombosis compared to APS with venous thrombosis, controls, and APS without thrombosis (p=0.03, p=0.0007, and p=0.0024 respectively). D allele frequency and D allele carrier state for VNTR were significantly less in APS than controls (p=0.0018 and p=0.0046 respectively).


CONCLUSIONS
C807T TT genotype may confer a risk for thrombosis and Kozak TC genotype for arterial thrombosis. D allele of VNTR may protect from APS. No patients with C807T TT or Kozak TC genotypes carried the protective DD genotype of VNTR. These polymorphisms may increase risk for both arterial and venous thrombosis. The utility of prophylaxis with anti-platelet drugs in at least a subgroup of APS patients should be investigated with clinical trials.
Istanbul University Istanbul Medical Faculty, Department of Internal Medicine, Division of Hematology. ipekyonal@yahoo.com.tr
Ipek
I
Yonal
Fehmi
F
Hindilerden
Veysel Sabri
VS
Hancer
Bahar
B
Artim-Esen
Aynur
A
Daglar
Basak
B
Akadam
Meliha
M
Nalcaci
Reyhan
R
Diz-Kucukkaya
D000328:Adult; D016736:Antiphospholipid Syndrome / Q000453:epidemiology* / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology* / Q000235:genetics*; D014421:Turkey / Q000453:epidemiology
D019038:Platelet Glycoprotein GPIb-IX Complex