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- Title
Susceptibility to chronic thromboembolic pulmonary hypertension may be conferred by miR- 759 via its targeted interaction with polymorphic fibrinogen alpha gene.
- Authors
Chen, Zhiyong; Nakajima, Toshiaki; Tanabe, Nobuhiro; Hinohara, Kunihiko; Sakao, Seiichiro; Kasahara, Yasunori; Tatsumi, Koichiro; Inoue, Yoshinori; Kimura, Akinori
- Abstract
deletion/insertion (Del/Ins) polymorphism of 28 base pairs (bp) in the 3′ untranslated region (UTR) of fibrinogen alpha gene ( FGA) was associated with thromboembolic diseases, but the underlying mechanisms remain unknown. Computational predication reveals that the 28 bp polymorphic fragment is complementary to the sequence of a microRNA, miR- 759. In this study, we aim to investigate the association and implicated mechanisms between FGA polymorphisms and the susceptibility to chronic thromboembolic pulmonary hypertension (CTEPH). The Del/Ins polymorphism was analyzed in 190 patients with CTEPH and 628 controls. The FGA 3′UTR and miR- 759 interaction was investigated using luciferase assay and quantitative RT-PCR method. Expression of miR- 759 and FGA in human tissues was investigated by RT-PCR. The results reveal that the allele frequency of Ins was significantly higher in the patients than in the controls (55.8 vs. 47.1%, P = 0.003, odds ratio = 1.42, 95% confidence interval: 1.13–1.79). Both miR- 759 and FGA were expressed in human liver. Co-transfection of miR- 759 decreased the expression and mRNA stability of reporter gene containing the FGA 3′UTR. The effect of miR- 759 was stronger on the Ins allele than on the Del allele. These observations suggest that the expression of FGA was regulated by miR- 759 through its interaction at the polymorphic 3′UTR sequence, which was associated with the susceptibility to CTEPH.
- Subjects
HYPERTENSION; GENETIC polymorphisms; PULMONARY hypertension; BLOOD circulation disorders
- Publication
Human Genetics, 2010, Vol 128, Issue 4, p443
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-010-0866-8