Impact of the Thr789Ala Variant of the von Willebrand Factor Levels, on Ristocetin Co-Factor and Collagen Binding Capacity and its Association with Coronary Heart Disease in Patients With Diabetes Mellitus Type 2

Abstract

A Thr789Ala variant in the von Willebrand Factor (vWF) gene is associated with increased vWF plasma concentrations and might therefore affect the risk of coronary heart disease (CHD) in the general population. Patients with type 2 diabetes have an increased risk for premature atherosclerosis and are characterized by alterations of the coagulation system. However, it is not known whether the Thr789Ala variant in the vWF gene contributes to the increased CHD risk in patients with type 2 diabetes. We therefore investigated the potential relationship between the Thr789Ala variant in the vWF gene and the occurrence of CHD in 356 patients with type 2 diabetes, either with (DM+/CHD+, n = 204) or without evidence for CHD (DM+/CHD-, n = 152). In addition, two control groups without type 2 diabetes, with (DM-/CHD+, n = 22) or without CHD (DM-/CHD-, n = 100), were investigated. Individuals with the vWF Thr789Ala variant have significantly higher von Willebrand factor plasma concentrations (p < 0.001). In addition, ristocetin co-factor was significantly increased in vWF Thr789Ala variant carriers (p < 0.05). Ristocetin co-factor levels and collagen binding capacity were also increased in individuals affected with either type 2 diabetes, CHD or both (DM+/CHD+, DM+/CHD-, DM-/CHD+) as compared to healthy controls (DM-/CHD-) (p < 0.001). However, we did not find an association between the vWF Thr789Ala variant and the occurrence of CHD in patient with type 2 diabetes (p = 0.34). In conclusion, although the Thr789Ala vWF gene variant is associated with increased plasma concentrations of vWF, ristocetin co factor levels and collagen binding capacity in patients with type 2 diabetes and CHD, a direct effect of this variant on the occurrence of CHD in patients with type 2 diabetes, could not be detected.

Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project

“…This finding confirms prior reports in healthy subjects and patients with diabetes of European ancestry 10,11,[30][31][32][33] and extends the p.Thr789Ala association to African-descent populations. rs1063856 (originally identified as an Rsa I restriction fragment length polymorphism) is in strong LD with rs1063857, which encodes a synonymous variant at p.Tyr795.…”

Genetic Risk Factors for Hepatopulmonary Syndrome in Patients With Advanced Liver Disease

“…One of these SNPs, rs1063856, encodes a missense variant (T789A) in exon 18 previously demonstrated to associate with higher circulating levels of VWF 27. In our cohort, possession of the alanine allele was significantly associated with case status (OR, 2.18; 95% confidence interval [CI]: 1.35–3.52, P =.002).…”

Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

“…This polymorphism has been associated with high VWF levels, and is close to SNP rs10638857 which is known to associate with VWF levels in healthy subjects. [24–26] We found the minor G-allele (rs 1063856) of the VWF gene to have some protective role in kidney function, but we were unable to conclude whether this favorable effect depends on modulation of plasma VWF levels.…”