title: rs2910164 Polymorphism Confers a Decreased Risk for Pulmonary Hypertension by Compromising the Processing of microRNA-146a.
abstract: OBJECTIVE
  To identify the association between rs2910164 polymorphism and development of pulmonary hypertension, as well as underlying molecular mechanism.
  
  
  RESULTS
  281 patients diagnosed with pulmonary hypertension and 325 normal controls were recruited, and rs2910164 genotype was determined in each participant: As a result, the rs2910164 polymorphism was significantly associated with the development of pulmonary hypertension after adjusting some potential confounding factors. Additionally, lung tissue samples were obtained from 39 patients who received surgical intervention for lung cancer, and mRNA and protein expression levels of miR-146a, COX-2 and PGI2 production were examined. Furthermore, we confirmed COX-2 is a target of miR-146a in pulmonary smooth muscle cells, and identified a differentially expressed miR-146a and COX-2 in each rs2910164 genotype group. We observed a significant association between rs2910164 polymorphism and the levels of either COX-2 or PGI2 using real-time PCR and western blot. In conclusion, the results of this study demonstrate that the rs2910164 CC and GC genotype is associated with a decreased risk of pulmonary hypertension, which could be attributed to defective miRNA processing and compromised ability to inhibit production of COX-2 and PGI2.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Liu
authors.forename: Mai
authors.initials: M
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Hexiang
authors.initials: H
authors.lastname: Cheng
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012323:RNA Processing, Post-Transcriptional
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs