DISEQUILIBRIUM IN EXPRESSION OF APOPTOSIS FACTORS BETWEEN SYMPTOMATIC AND ASYMPTOMATIC INDIVIDUALS WITH ACUTE INTERMITTENT PORPHYRIA

Elisabeth I. Minder, Anna-Elisabeth Minder and Xiaoye Schneider-Yin

Stadtspital triemli, Zürich, Switzerland

Deficiency in hydroxymethylbilane synthase (HMBS) is the primary cause of acute intermittent porphyria (AIP) – a dominantly inherited disorder. However, not all individuals with a defective enzyme develop AIP symptoms. To explore the mechanism of incomplete penetrance in AIP, we generated gene expression profiles from AIP patients (n=6), asymptomatic mutation carriers (n=3) and control subjects (n=3). Among the 6 patients studied, 3 suffered from more than 3 episodes of acute attacks in the past and were categorized as “severe symptomatic”. RNA samples were prepared from peripheral blood and then hybridized with Microarray U133A chips. Expression data obtained from Microarray correlated with clinical statuses as analyzed by hierarchical tree clustering. If the samples are grouped based on clinical statuses, 1040 genes (p=0.05), 2005 genes (p=0.1) respectively, out of 15’914 genes tested were found to be differentially expressed. The highest percentage of differentially expressed genes were found in the categories “apoptosis regulators” and “cell death regulators” from genebank “Simplified Gene Ontology”. Factors from both intrinsic and extrinsic apoptosis pathways were involved. These results suggest that expression level of various apoptosis factors correlate with the clinical penetrance of AIP.