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.448G4A g.501C4T g.764T4C g.2267A4T g.2390C4T g.3144T4C g.3912A4G g.4857A4G). In the coding regions, a single alteration in the 3 0 untranslated region in exon 7 (g.8129T4C) 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.

Identification of candidate colon cancer biomarkers by applying a random forest approach on microarray data

“…It was confirmed that IL8 is differentially expressed in colon cancer, and is associated with proliferation, migration, angiogenesis and chemosensitivity in colon cancer cell line models (30). The VIP gene has also been the focus of investigation in many studies ralating to human cancer (31)(32)(33)(34)(35)(36). WDR77, also known as p44, was reported to be related to the differentiation and proliferation in prostate epithelium (37).…”

Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future

“…Knockout of VIP in the mouse produces a pulmonary hypertension phenotype that can be reversed by a 4-week infusion of VIP (Said et al, 2007). A polymorphism in the coding region of exon 7 (g.8129T4C) has been reported with a similar frequency distribution in Caucasians with and without PAH (50% vs 46%) (Haberl et al, 2007) but is perhaps more common in Chinese with PAH (40.7%) compared to controls (15.2%) (Y. . Serum VIP levels were numerically lower and pulmonary haemodynamics worse in the PAH patients with this variant (n=33) than those without (n=48), but the biological differences were only small, and so the clinical significance is uncertain(Y. .…”

Role of Vasoactive Intestinal Peptide in Chronic Obstructive Pulmonary Disease with Pulmonary Hypertension

“…Knockout mice lacking the VIP gene or humans presenting polymorphism of sequences encoding VIP are affected by PAH, [17][18][19] as are patients with an underexpression of constitutive secretion of NO. 20 Thus, a diminution of VIP was expected; however, the measurement showed an unexpected and interesting increase.…”