Contribution of coagulation factor VII R353Q, 2323P0/10 and HVR4 polymorphisms to coronary artery disease in Tunisians Sonia Ben-Hadj-Khalifa • Basma Lakhal • Touhami Mahjoub • Wassim Y. Almawi Published online: 30 August 2012 Ó Springer Science+Business Media, LLC 2012 Abstract We examined the contribution of two factor VII (FVII) bi-allelic (R353Q, -323P0/10) and one tandem repeat (HVR4) polymorphisms to the risk of coronary artery disease (CAD) in Tunisians. Study subjects comprised 308 CAD patients and 312 age-, gender- and ethnically-matched controls. Regression analysis was used in assessing the FVII association to CAD risk. While the distribution of -323P0/ 10 alleles and genotypes were comparable between cases and controls, marginal association of the R353Q variant was noted, with the Q allele (19.1 vs. 23.8 %; P = 0.05) and Q allele-containing genotypes (R/Q ? Q/Q; 33.8 vs. 48.0 %) being slightly under-represented in cases than in controls. On the other hand, four alleles of FVII microsatellite HVR4 were detected at variable frequencies in Tunisians, and comprised H6 (63.2 %), H7 (33.8 %), and to lesser extents H5 (1.9 %) and H8 (0.8 %). Of these, the H7 variant was under-represented in patients [P = 0.038; OR (95 %CI) = 0.75 (0.58–0.97)]. Of the major genotypes detected (H6/H6, H6/H7, H7/H7) only H6/H6 was positively associated with CAD [P = 0.047; OR (95 %CI) = 1.39 (1.00–1.94)]. In conclusion, our study underscores the role of polymorphisms in the FVII gene in modulating the sus- ceptibility to CAD in (North African) Tunisian Arabs. Keywords Coronary artery disease Á Factor VII Á Polymorphisms Á Risk factor Introduction Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide, being the consequence of rupture/fissure of atherosclerotic plaque and thrombus development [1]. Vascular injury caused by damage to the blood vessels endothelial lining stimulates tissue factor (TF) blood exposure, and subsequently its binding to cir- culating factor VII (FVII) [2, 3], which then binds TF with high affinity and specificity [4]. FVII rapidly converts to activated FVIIa [3], which then binds factor X, resulting in its conversion to activated factor Xa, leading eventually to thrombin activation and clot formation [3, 5, 6]. Activation of the extrinsic pathway of coagulation plays a major role in CAD pathogenesis and clinical and experimental studies support the notion that TF/FVIIa complex is the main initiator of the coagulation cascade in cardiovascular dis- ease [7], and that FVII circulating levels influence the severity of CAD [8]. A number of studies documented elevated FVII levels with increased cardiovascular risk [9–11]. Plasma con- centrations of FVII are influence by both non-genetic (environmental) and genetic factors, the latter including the functional variants R353Q (rs6046) and the promoter decanucleotide insertion/deletion polymorphism -323P0/ 10 (rs36208070), which were associated with marked reduction in plasma FVII levels [12, 13] which were in linkage disequilibrium [14]. Studies investigating the contribution of the R353Q and -323P0/10 FVII variants have been inconclusive, with some studies demonstrating protective effect of the 353Q variant [15–17], while others S. Ben-Hadj-Khalifa Á T. Mahjoub Faculty of Pharmacy, Research Unit of Biology and Genetics of Hematologic and Autoimmune Diseases, Monastir, Tunisia B. Lakhal Cytogenetics and Biology Department, Farhat Hached University Teaching Hospital, Sousse, Tunisia W. Y. Almawi (&) Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain e-mail: wassim@agu.edu.bh 123 J Thromb Thrombolysis (2013) 35:243–249 DOI 10.1007/s11239-012-0800-0