A Common Genetic Polymorphism (46 C to T Substitution) in the 5′-Untranslated Region of the Coagulation Factor XII Gene Is Associated With Low Translation Efficiency and Decrease in Plasma Factor XII Level
Open Access
- 15 March 1998
- journal article
- Published by American Society of Hematology in Blood
- Vol. 91 (6) , 2010-2014
- https://doi.org/10.1182/blood.v91.6.2010
Abstract
We studied the Hga I polymorphism (46 C/T) in the 5′-untranslated region of the coagulation factor XII (FXII) gene corresponding to four bases upstream from the ATG translation initiation codon. By using allele-specific restriction analysis with restriction endonuclease Hga I, the allele frequency of 46C/T was estimated to be 0.27/0.73 in Orientals (allele number =152), and conversely, 0.8/0.2 in Caucasians (allele number =40). Because it has been reported that plasma levels of FXII were lower in Orientals than in Caucasians, we investigated the relationship between this polymorphism and plasma levels of FXII. As a result, there were significant differences in plasma FXII levels between these three allele types: C/C,170±38% (178±27%); C/T, 141±29% (123±34%); and T/T, 82±19% (61±11%) [FXII activity (FXII antigen levels)]. In heterozygotes of 46 C/T both alleles were equally transcribed in hepatocytes, as determined by reverse transcription polymerase chain reaction (RT-PCR), suggesting little influence of the polymorphism at the level of transcription or on the stability of mRNA. In in vitro transcription/translation analysis, less FXII was produced from cDNA containing 46 T than from that containing 46 C. Therefore, it is highly likely that the 46 T polymorphism in the FXII gene decreased the translation efficiency and led to low plasma levels of FXII activity and antigen, probably due to the creation of another ATG codon and/or impairment of the consensus sequence for the translation initiation scanning model.Keywords
This publication has 16 references indexed in Scilit:
- Human Gene Mutations Affecting RNA Processing and TranslationAnnals of Medicine, 1993
- Role of the Contact System in FibrinolysisSeminars in Thrombosis and Hemostasis, 1987
- Contact Factors in Health and DiseaseSeminars in Thrombosis and Hemostasis, 1987
- cDNA sequence coding for human coagulation factor XII (Hageman)Nucleic Acids Research, 1986
- Characterization of a cDNA coding for human factor XII (Hageman factor)Biochemistry, 1986
- Thrombosis or Myocardial Infarction in Congenital Clotting Factor Abnormalities and Chronic ThrombocytopeniasMedicine, 1983
- Reduced Titers of Hageman Factor (Factor XII) in OrientalsAnnals of Internal Medicine, 1981
- Structural Changes Accompanying Enzymatic Activation of Human Hageman FactorJournal of Clinical Investigation, 1974
- Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodiesAnalytical Biochemistry, 1966
- A FAMILIAL HEMORRHAGIC TRAIT ASSOCIATED WITH A DEFICIENCY OF A CLOT-PROMOTING FRACTION OF PLASMA 1Journal of Clinical Investigation, 1955