Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence than ethnicity?

Abstract

The Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ϰ² values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ϰ² value) than between Basques and controls (1,570 cumulated ϰ² value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p< 0.0004). This is mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V Leiden prevalence does not differ. Numerous other differences covering a wide range of proteins of the haemostaseome may result in an overall different genetic risk for venous thromboembolism.

Why is factor V Leiden so rare in the Basques?

“…Therefore, the low prevalence of FVL in Basques results probably from the combination of various elements: a pre-Neolithic individualization with subsequent little mixing with populations in which this polymorphism is prevalent, the effect of genetic drift and the absence of significant selective pressure regarding iron deficiency because of a prolonged exposure to the iron-rich Paleolithic diet. Besides the rarity of FVL, Basques demonstrate a particular genetic profile regarding the hemostatic system ('hemostaseome') [19]. Intriguingly, they seem to express a series of favorable biological characteristics that may protect against venous thrombosis [20].…”