Factor XIII-A Val34Leu and Tyr204Phe variants influence clot kinetics in a cohort of South African type 2 diabetes mellitus patients

• Published in: Gene Vol. 834; p. 146637
• Main Authors: Phasha, M.N., Soma, P., Bester, J., Pretorius, E., Phulukdaree, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-08-2022
• Subjects: Coagulation; Factor XIII; Polymorphism; Type 2 Diabetes Mellitus; Val; T2DM; α-angle; NAFLD; Factor XIII; TTG; Coagulation; Kcat/Km; WB; K; Pro; Phe; bp; RPL; PPP; R; SNP; MA; Type 2 Diabetes Mellitus; HWE; Lys 30; RFLP; gDNA; OR; tPA; CI; dNTPs; Tyr; TMRTG; Factor XIII-A; CVD; RE; TEG; PAI; MRTG; Leu; VT; PCR; Polymorphism
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146637

•A significant association between the Val34Leu polymorphism and T2DM was found.•The 204Phe variant was more prevalent in controls compared to T2DM.•A hypo-coagulable clot profile but stronger clot of platelet poor plasma was observed in T2DM.•Higher clot strength and resistance was observed in the presence of the 34Leu variant.•The presence of the 204Phe variant in T2DM influenced clot kinetics.
Factor XIII, a transglutaminase that plays a crucial role in clot formation, consists of subunits A and B. Single nucleotide polymorphisms in Factor XIII-A have been linked to thrombotic risk. In Type 2 Diabetes mellitus (T2DM), a hypercoagulable state is thought to contribute to the high mortality rate associated with thrombotic diseases. Due to the lack of prevalence data of FXIII-A single nucleotide polymorphisms (SNPs) in T2DM in a South African cohort, this study assessed the prevalence FXIII-A Val34Leu (rs5985) and Tyr204Phe (rs3024477) SNP’s and the effect on clot kinetics in T2DM.
A cohort of T2DM patients (n = 100) and race, age and gender matched healthy controls (n = 101) were recruited following ethical approval. Thromboelastography® (TEG®) was used to assess the viscoelastic properties in platelet poor plasma (PPP) in controls (n = 91) and T2DM patients (n = 91) younger than 50 years old. Genomic DNA was isolated from whole blood using the Quick-DNA™ Miniprep Plus Kit and PCR-RFLP was used to genotype each sample for FXIII-A rs5985 and rs3024477 SNPs.
TEG® analyses indicated a longer R-time (p < 0.0001) and higher TMRTG (p < 0.0001) in PPP of T2DM patients. Control and T2DM genotype distribution conformed to Hardy-Weinberg equilibrium (p > 0.05). There was a higher prevalence of the wildtype genotype of FXIII-A Tyr204Phe (rs3024477) SNP in T2DM (OR = 0.23, 95% CI = 0.12–0.42, p < 0.0001). The 204Phe variant was more frequent in the Caucasians (OR = 0.39, 95% CI = 0.05–0.33, p < 0.0001). The presence of the 204Phe variant in T2DM affected TMRTG (p = 0.0207). The variant affected R time (p = 0.0432) and TMRTG (p = 0.0209 and p = 0.0207) in controls and T2DM, respectively.
An inverse association with T2DM and FXIII-A Tyr204Phe was found. A hypo coagulable PPP clot profile was observed in T2DM. A shorter reaction time was observed and but faster rate at which the clot reached maximum strength in both controls and T2DM in the presence of the 204Phe variant.