title: 5'UTR repeat polymorphisms of the BMPR2 gene in children with pulmonary hypertension associated with congenital heart disease.
abstract: The mutations of bone morphogenetic protein receptor type 2 (BMPR2) in patients with idiopathic pulmonary hypertension has been well defined. We investigated the occurrence of BMPR2 mutation and genetic polymorphisms in children with pulmonary hypertension associated with congenital heart disease (aPH/CHD) and correlated with the pulmonary haemodynamic and vasoreactivity.
  
  
  METHODS
  BMPR2 mutation/polymorphisms were determined in 30 aPH/CHD children. All children underwent cardiac catheterisation to obtain baseline haemodynamic data. The 5'UTR containing promoter region and all the exons [1-13] of BMPR2 gene were genotyped for possible genetic variants that may be related to the aPH/CHD.
  
  
  RESULTS
  None of our 30 patients (median-age 90 months) with aPH/CHD (mean PAP 48±17mmHg, PVR 6.7±4.2WUm(2)) has had any BMPR2 mutation. Fifteen of them had single nucleotide polymorphism, rs1061157 and/or 5'UTR-polymorphism, specifically GGC repeat variant in seven patients; AGC repeat variant in one patient; and nine base pairs duplication (CTTCTTCGG) in one patient. The GGC repeat ≥13 was found in three out of six of children with aPH/CHD with normal PVR vs. two out of 24 children with aPH/CHD with high PVR. The odd ratio between these two subgroups of aPH/CHD is 0.09 (95% CI 0.02-0.34).
  
  
  CONCLUSIONS
  In our cohort, there was no BMPR2 mutation in children with aPH/CHD while nine out of 30 of them have 5'UTR repeat polymorphisms. Our data suggests the occurrence of GGC repeat ≥13 at the 5'UTR region may have some protective effect towards pulmonary vasculopathy in children who have been exposed to high pulmonary blood flow due to CHD.
authors.affiliation: Division of Pediatric Cardiology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. alimsuwan@yahoo.com
authors.forename: Alisa
authors.initials: A
authors.lastname: Limsuwan
authors.forename: Lulin
authors.initials: L
authors.lastname: Choubtum
authors.forename: Duangrurdee
authors.initials: D
authors.lastname: Wattanasirichaigoon
mesh_terms: D000293:Adolescent; D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000151:congenital / Q000235:genetics*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D020079:Terminal Repeat Sequences; D018911:Trinucleotide Repeats; D014655:Vascular Resistance / Q000235:genetics; D055815:Young Adult
chemical_list: C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II