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Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs
Author(s) -
Vossen Carla Y.,
Hylckama Vlieg Astrid,
TeruelMontoya Raúl,
SalloumAsfar Salam,
Haan Hugoline,
Corral Javier,
Reitsma Pieter,
Koeleman Bobby P. C.,
Martínez Constantino
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14629
Subject(s) - untranslated region , single nucleotide polymorphism , genetics , gene , biology , snp , microrna , three prime untranslated region , linkage disequilibrium , coagulation , factor v , venous thrombosis , tissue factor , genotype , medicine , thrombosis , messenger rna
Summary Micro RNA s have been recognized as critical regulators of gene expression and might affect the risk of venous thrombosis. We aimed to identify 3′ untranslated region ( UTR ) variants in coagulation genes that influence coagulation factor levels and venous thrombosis risk. The 3′ UTR of coagulation genes were sequenced in subjects with extremely high or low plasma levels of these factors in two case‐control studies. In total, 28 variants were identified. Five single nucleotide polymorphisms ( SNP s) were predominantly present in one extreme level group ( F2 rs1799963, F8 rs1050705 and F11 rs4253429, rs4253430 and rs1062547). Additional to F2 rs1799963, F8 rs1050705 (in men) and F11 rs4253430 were associated with an increased risk of venous thrombosis albeit confidence intervals were wide. The three F11 SNP s were in high linkage disequilibrium with functional variants rs2289252 and rs2036914. Rs1062547 and rs4253430 were associated with a significant increase of plasma FXI activity in heterozygotes and homozygotes in wild‐type controls. In silico prediction revealed that these SNP s might disturb the binding sites of miR‐544 and miR‐513a‐3p. Only miR‐544 provoked a significant decrease of the luciferase activity that was not observed with a rs4253430 mutated vector. In conclusion, these results reinforce that micro RNA s are candidates to play a role in haemostasis and complex disorders, such as thrombosis.