ISSN: 1300-7777 E-ISSN: 1308-5263
Association of FXII 5’UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease [Turk J Hematol]
Turk J Hematol. 2010; 27(1): 15-19

Association of FXII 5’UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease

Parisa Rasighaemi1, Ahmad Kazemi1, Fereidun Ala2, Mohammad Jazebi3, Farnaz Razmkhah1
1Department Of Hematology, Iran University Of Medical Sciences, Tehran, Iran
2National Blood Transfusion Service, Birmingham, United Kingdom
3Centre Of Pediatric Hemophilia, Tehran, Iran

OBJECTIVE: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. Plasma FXII activity levels are strongly determined by a 46CγT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study.
METHODS: One hundred and sixty subjects were studied: 120 patients diagnosed with thrombophilia (96 venous thromboembolism, 24 arterial thrombosis), and 40 age-gender-matched controls. For each subject, FXII activity level was measured by a one-step clotting assay with FXII-deficient plasma, and 46CγT polymorphism was genotyped using a restriction fragment length polymorphism (RFLP) method.
RESULTS: In this study, the previous observation that individuals with different genotypes for the 46 CγT polymorphism showed significant differences in Factor XII activity levels was confirmed. Most importantly, FXII activity ≤ 68% was associated with an increased risk of venous thrombosis with an adjusted OR of 4.7 (95%CI= 1.03-21.1, P=0.04). However, it was not a risk factor for arterial thrombosis with adjusted OR of 5 (95%CI= 0.91-27.1, P=0.09). In CT and TT genotype the adjusted ORs were respectively 2 (95%CI=0.9-4.4, P=0.11) and 2.3 (95%CI=0.45-11, P=0.48) for patients with venous thrombosis compared with the controls. Similarly, the adjusted ORs in arterial thrombosis were 1.2 (95%CI=0.4-3.6, P=0.76) for CT and 1.8 (95%CI=0.2-14.9, P=0.59) for TT genotype. Thus, we did not find any association of the mutated T allele in the heterozygous or homozygous state with an increased risk of both venous and arterial thrombosis.
CONCLUSION: Lower FXII activity is not a risk factor; rather, it simply represents a risk marker for thrombosis.

Keywords: Factor XII, factor XII polymorphism, venous thromboembolism, arterial thrombosis


FXII 5'UTR 46C>T polimorfizmi ile FXII aktivitesi ve trombotik hastalık riskinin ilişkisi

Parisa Rasighaemi1, Ahmad Kazemi1, Fereidun Ala2, Mohammad Jazebi3, Farnaz Razmkhah1
1
2
3

AMAÇ: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in the pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. One of the most important determinants of Plasma FXII level is 46CgT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study.
YÖNTEMLER: Yüz altmış denek incelenmiştir: 120 hastaya trombofili (96’sı tromboembolizm, 24’ü arteriyel tromboz) tanısı konmuş olup 40 hasta yaş ve cinsiyet açısından eşleştirilmiştir. Her bir denek için, FXII aktivite düzeyi, FXII’den yoksun plazma ile tek adımlı pıhtılaşma testi kullanarak ölçülmüş ve 46CγT polimorfizmi, (RFLP) yöntemi ile genotiplenmiştir.
BULGULAR: 46 CγT polimorfizmi için farklı genotipleri olan bireylerin FXII aktivite düzeylerinde anlamlı farklılıklar sergilediğine dair önceki gözlem, bu çalışmada doğrulanmıştır. Daha da önemlisi, ≤%68 olan FXII aktivitesi, 4.7 ayarlanmış risk oranı (OR) ile venöz tromboza yönelik yüksek risk ile ilişkilendirilmiştir (%95 güven aralığı [CI]: 1.03-21.1, p=0.04). Ancak bu, 5 ayarlanmış OR ile arteriyel tromboza yönelik bir risk faktörü değildir (%95 CI: 0.91-27.1, p=0.09). Ct ve TT genotipte, ayarlanmış OR değerleri, kontrollere kıyasla venöz trombozlu hastalar için sırasıyla 2 (%95 CI: 0.9-4.4, p=0.11) ve 2.3 (%95 CI: 0.45-11, p=0.48) idi. Benzer şekilde, arteriyel trombozda ayarlanmış OR değerleri CT genotip için 1.2 (%95 CI: 0.4 - 3.6, p=0.76) ve TT genotip için 1.8 (%95 CI: 0.2-14.9, p=0.59) idi. Böylelikle, heterozigot veya homozigot halde mutasyona uğramış T aleli ile venöz ya da arteriyel tromboza ilişkin yüksek risk arasında herhangi bir ilişki tespit edilmemiştir.
SONUÇ: Düşük FXII aktivitesi bir risk faktörü olmamakla birlikte, yalnızca tromboza yönelik bir risk göstergesini temsil etmektedir.

Anahtar Kelimeler: Faktör XII, faktör XII polimorfizm, venöz tromboembolizm, arteriyel tromboz


Parisa Rasighaemi, Ahmad Kazemi, Fereidun Ala, Mohammad Jazebi, Farnaz Razmkhah. Association of FXII 5’UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease. Turk J Hematol. 2010; 27(1): 15-19

Corresponding Author: Ahmad Kazemi, Iran


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