1. ¹Medical University of Vienna, Department of Internal Medicine I, Division Institute of Cancer Research, Borschkegasse 8a, Vienna A-1090, Austria
2. ²Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
3. ³Department of Internal Medicine IV, Division of Pulmonary Medicine, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
4. ⁴Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
5. ⁵Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
6. ⁶Department of Histology, Medical University of Vienna, Waehringerstr. 13a, Vienna A-1090, Austria

Correspondence: W Mosgoeller, Department of Internal Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, Vienna A-1090, Austria. Tel: +43 1 4277 65260; Fax: +43 1 4277 65264; E-mail: wilhelm.mosgoeller@meduniwien.ac.at

Received 28 February 2006; Revised 1 August 2006; Accepted 2 August 2006; Published online 27 September 2006.

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.