Polymorphism rs2066865 in the Fibrinogen Gamma Chain (FGG) Gene Increases Plasma Fibrinogen Concentration and Is Associated with an Increased Microvascular Thrombosis Rate

Abstract

Background and Objective: Thrombosis due to inherited hypercoagulability is an issue that has been raised in microvascular flap surgery previously. We analyzed the association of a single nucleotide polymorphism (SNP) in rs2066865 in the fibrinogen gamma chain (FGG) gene, alteration in plasma fibrinogen concentration, and presence of microvascular flap thrombosis. Materials and Methods: A total of 104 adult patients with microvascular flap surgery were subjected to an analysis of the presence of SNP rs2066865 in the FGG gene. Alterations in plasma fibrinogen concentration according to genotype were determined as a primary outcome, and flap thrombosis was defined as a secondary outcome. Results: Flap thrombosis was detected in 11.5% of patients (n = 12). Successful revision of anastomosis was performed in four patients, resulting in a microvascular flap survival rate of 92.3%. We observed an increase in plasma fibrinogen concentration in genotype G/A and A/A carriers (G/G, 3.9 (IQR 4.76-3.04); G/A, 4.28 (IQR 5.38-3.18); A/A, 6.87 (IQR 8.25-5.49) (A/A vs. G/A, p = 0.003 and A/A vs. G/G, p = 0.001). Within group differences in microvascular flap thrombosis incidence rates were observed—G/G 6/79 (7.59%); G/A 5/22 (22.7%); A/A 1/3 (33.3%) (OR 0.30 95%; CI 0.044 to 0.57), p = 0.016; RR 3.2—when G/G versus G/A and A/A were analyzed respectively. Conclusions: A/A and G/A genotype carriers of a single nucleotide polymorphism in rs2066865 in the fibrinogen gamma chain gene had a higher plasma fibrinogen concentration, and this might be associated with an increased microvascular flap thrombosis incidence rate. Determined polymorphism could be considered as a genetic marker associated with microvascular flap thrombosis development. To confirm the results of this study, the data should be replicated in a greater sample size.

Fibrinogen and Atherosclerotic Cardiovascular Diseases—Review of the Literature and Clinical Studies

“…There are also newer studies, the results of which indicate a significant role of the FGG polymorphism in the risk of CVD. In a study by Drizlionok et al A/A and G/A genotype carriers of an SNP in rs2066865 in the FGG had a higher plasma fibrinogen concentration, and this might be associated with an increased risk of microvascular thrombosis [ 75 ].…”

Thromboelastometry for Assessing Risks of Free Flap Thrombosis in Patients Undergoing Microvascular Surgery

“…Anyhow, we were not able to avoid the multifactorial nature of a thrombotic event and the human factor in surgery and postoperative care. In microvascular flap thrombosis, both the arterial and venous pools may play a role, which is further augmented by the genetic background of the patients (47,48) or acquired thrombophilia. Therefore, we warrant an appropriate thrombotic risk assessment score for microvascular surgery patients.…”

A genetic study of FGG/FGA‎ mutations effect on D-dimer levels among COVID-19 patients in Jordan

“…It was proposed that it might start the coagulation cascade that results in the development of brin clots when its expression rises in response to tissue damage or in ammation. The 261 COVID-19 patients who participated in the previous study showed that individuals with the factor III mutation had signi cantly higher D-dimer levels than those without the mutation [12]. Patients who had the factor III mutation were more likely to pass away than those who did not have the mutation.…”

“…Its molecules are 45nm long structures that are composed of two sets of three polypeptide chains: A alpha; B beta; and gamma [11]. Each of these chains is encoded by a separate gene namely, brinogen alpha (FGA), brinogen beta (FGB), and brinogen gamma (FGG), clustered in a region of approximately 50 kb on chromosome 4q31.3 [12]. FGG and FGA are components of brinogen, which are soluble plasma proteins that coagulate into insoluble brin [10].…”