Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population

Speranza Rubattu; Emanuele Di Angelantonio; Dorothea Nitsch; Bruna Gigante; Bastianina Zanda; Rosita Stanzione; Anna Evangelista; Angelo Pirisi; Giulio Rosati; Massimo Volpe

doi:10.1160/TH04-07-0457

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(06): 1095-1100
DOI: 10.1160/TH04-07-0457

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population

Authors

Speranza Rubattu

¹IRCCS Neuromed, Pozzilli (Is), University La Sapienza, Ospedale Sant’Andrea, Rome, Italy

²Department of Cardiology, II^nd School of Medicine, University La Sapienza, Ospedale Sant’Andrea, Rome, Italy
Emanuele Di Angelantonio

³Department of Internal Medicine, I^st School of Medicine, University La Sapienza, Rome, Italy
Dorothea Nitsch

⁴Dept of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, U. K.
Bruna Gigante

⁵Dept. of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy
Bastianina Zanda

⁶Institute of Clinica Neurologica, University of Sassari, Italy
Rosita Stanzione

¹IRCCS Neuromed, Pozzilli (Is), University La Sapienza, Ospedale Sant’Andrea, Rome, Italy
Anna Evangelista

¹IRCCS Neuromed, Pozzilli (Is), University La Sapienza, Ospedale Sant’Andrea, Rome, Italy
Angelo Pirisi

⁶Institute of Clinica Neurologica, University of Sassari, Italy
Giulio Rosati

⁶Institute of Clinica Neurologica, University of Sassari, Italy
Massimo Volpe

¹IRCCS Neuromed, Pozzilli (Is), University La Sapienza, Ospedale Sant’Andrea, Rome, Italy

²Department of Cardiology, II^nd School of Medicine, University La Sapienza, Ospedale Sant’Andrea, Rome, Italy

Abstract

Summary

Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the Factor VII G10976A and –C122T polymorphisms on the susceptibility to develop IS in a genetically homogenous and clinically well ascertained case-control study including 294 cases (median age 75 years; 176 males/118 females) and 286 controls (median age 73 years; 163 males/123 females) in Sardinia, Italy. In addition, we carried out an exploratory analysis with respect to other frequently studied polymorphisms of haemostatic factor genes: Factor II G20210A, Factor V G1691A,, Fibrinogen α-chain Thr312Ala, Fibrinogen β-chain –C148T, Factor XIII G185T, GPIIb/IIIa T1565C. Among all the genes tested, FVII –C122T showed a significant, independent contribution to IS predisposition both in crude and adjusted analyses (crude OR 1.52, 95% CI 1.09–2.10, P=0.013; adjusted OR 1.48, 95% CI 1.04–2.09, P=0.028, respectively). Haplotype analyses revealed a conserved population structure with high linkage disequilibrium between both FVII mutations tested. Blood levels of FVII had an inverse relationship with the polymorphism involved. Apart from genetic influence, there was a significant role for hypertension (OR=1.7, 95% CI 1.19–2.43, P=0.003), hypercholesterolemia (OR=2.21, 95% CI 1.38–3.54, P=0.001) and atrial fibrillation (OR=1.66, 95% CI 1.06–2.58, P=0.026) on IS occurrence. In summary, we describe evidence for a possible direct association of FVII gene molecular variants with the occurrence of IS in a genetically homogenous human sample.

Keywords

Stroke - genetics - coagulation factors - polymorphisms

Full Text

References

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