title: Vasoactive intestinal peptide gene alterations in patients with idiopathic pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension is a progressive disease, characterised by increased proliferation of pulmonary artery smooth muscle cells, vasoconstriction and remodelling of the vascular wall leading to right heart failure and death. The idiopathic form is rare (idiopathic arterial primary hypertension (IPAH); formerly PPH, MIM# 178600). Our group correlated a deficiency in vasoactive intestinal peptide (VIP; MIM# 192320) levels in serum and lung tissue with the pathogenesis of IPAH. The aim of this study was to investigate the relevance of genetic alterations in VIP to the development of IPAH. We screened 10 patients (age 4-66 years) for alterations in the coding, the noncoding regions and the enhancer region of the VIP gene by direct sequencing. In eight of 10 patients, we found alterations compared to the wild-type sequence. We detected nine alterations. In the noncoding regions, eight alterations were in the introns 1, 2, 3 and 4 (g.448G>A g.501C>T g.764T>C g.2267A>T g.2390C>T g.3144T>C g.3912A>G g.4857A>G). In the coding regions, a single alteration in the 3' untranslated region in exon 7 (g.8129T>C) was observed in five patients. It appeared in 46% of the control group. The frequency of this alteration in the coding region of the VIP gene could therefore not be correlated with the appearance of IPAH. Apart from the importance of VIP signalling, genetic and/or environmental modifiers might therefore contribute to the development and perpetuation of the disease.
authors.affiliation: Medical University of Vienna, Department of Internal Medicine I, Division Institute of Cancer Research, Borschkegasse 8a, Vienna A-1090, Austria.
authors.forename: Ines
authors.initials: I
authors.lastname: Haberl
authors.forename: Klemens
authors.initials: K
authors.lastname: Frei
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ramsebner
authors.forename: Daniel
authors.initials: D
authors.lastname: Doberer
authors.forename: Ventzislav
authors.initials: V
authors.lastname: Petkov
authors.forename: Sulaima
authors.initials: S
authors.lastname: Albinni
authors.forename: Irene
authors.initials: I
authors.lastname: Lang
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Mosgoeller
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D007438:Introns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D014660:Vasoactive Intestinal Peptide / Q000097:blood / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D014660:Vasoactive Intestinal Peptide