PMID- 35671883
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20220623
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 834
DP  - 2022 Aug 5
TI  - Factor XIII-A Val34Leu and Tyr204Phe variants influence clot kinetics in a cohort 
      of South African type 2 diabetes mellitus patients.
PG  - 146637
LID - S0378-1119(22)00456-5 [pii]
LID - 10.1016/j.gene.2022.146637 [doi]
AB  - 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. MATERIALS AND METHODS: 
      A cohort of T2DM patients (n = 100) and race, age and gender matched healthy 
      controls (n = 101) were recruited following ethical approval. 
      Thromboelastography(R) (TEG(R)) 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. RESULTS: TEG(R) 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. CONCLUSION: 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.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Phasha, M N
AU  - Phasha MN
AD  - Department of Physiology, School of Medicine, Faculty of Health Sciences, 
      University of Pretoria, Gauteng, South Africa.
FAU - Soma, P
AU  - Soma P
AD  - Department of Anatomy, School of Medicine, Faculty of Health Sciences, University 
      of Pretoria, Gauteng, South Africa.
FAU - Bester, J
AU  - Bester J
AD  - Department of Physiology, School of Medicine, Faculty of Health Sciences, 
      University of Pretoria, Gauteng, South Africa.
FAU - Pretorius, E
AU  - Pretorius E
AD  - Department of Physiological Sciences, School of Medicine, Faculty of Health 
      Sciences, Stellenbosch University, Western Cape, South Africa.
FAU - Phulukdaree, A
AU  - Phulukdaree A
AD  - Department of Physiology, School of Medicine, Faculty of Health Sciences, 
      University of Pretoria, Gauteng, South Africa. Electronic address: 
      alisa.phulukdaree@up.ac.za.
LA  - eng
PT  - Journal Article
DEP - 20220604
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 839MOZ74GK (F8 protein, human)
RN  - 9001-27-8 (Factor VIII)
RN  - 9013-56-3 (Factor XIII)
RN  - EC 2.3.2.13 (Factor XIIIa)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Factor VIII/*genetics
MH  - Factor XIII/genetics
MH  - Factor XIIIa/genetics
MH  - Humans
MH  - Kinetics
MH  - Middle Aged
MH  - South Africa
MH  - *Thrombosis/genetics
OTO - NOTNLM
OT  - Coagulation
OT  - Factor XIII
OT  - Polymorphism
OT  - Type 2 Diabetes Mellitus
EDAT- 2022/06/08 06:00
MHDA- 2022/06/22 06:00
CRDT- 2022/06/07 19:25
PHST- 2021/12/01 00:00 [received]
PHST- 2022/05/10 00:00 [revised]
PHST- 2022/06/02 00:00 [accepted]
PHST- 2022/06/08 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/06/07 19:25 [entrez]
AID - S0378-1119(22)00456-5 [pii]
AID - 10.1016/j.gene.2022.146637 [doi]
PST - ppublish
SO  - Gene. 2022 Aug 5;834:146637. doi: 10.1016/j.gene.2022.146637. Epub 2022 Jun 4.