P1 Hamp Gene Allelic Variants in Porphyria Cutanea

MEDINA, NANCY; COLOMBO, FEDERICO; LAVANDERA, JIMENA; ROSSETTI, MARIA VICTORIA; BATLLE, ALCIRA; PARERA, VICTORIA

Lucerna

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS; 2013

Porphyria cutanea tarda (PCT) is a metabolic disorder produced by a diminished URO-D activity. It is precipitated by various ecogenic factors such as iron overload, alcohol, polyhalogenated hidrocarbons, estrogens, and its association with hepatitis C virus and HIV infection. Hereditary Hemochromatosis (HH) is an iron overload syndrome caused by increased duodenal iron absorption, which leads to excessive iron deposition in parenchymal cells of the liver and mayor organs, causing cirrhosis, diabetes, cardiac failure, endocrine complications and arthritis. There are 6 types of HH related to mutations in the genes that encode proteins of iron metabolism being HFE gene responsible of HH type I and HAMP gene responsible of type IIB. Hepcidin, codified by HAMP plays a key role of iron homeostasis. The aim was to study the prevalence of genetic variations in HAMP that could influence PCT triggering. The three exons, splicing sites and promotor regions of HAMP were amplified and sequenced in 37 PCT patients without mutations in HFE gene. Two polymorphisms already reported were detected: nc.-153C > T, only in one PCT case (2,7 % ) and nc.-582A > G in 14 PCT (38 % ). In other four groups, the promoter was analized by RFLP for nc.- 582A > G variant: 1 and 2) subjects with clinical HH, with and without mutations in HFE (n = 13 and 17 respectively); 3) control group (n = 50); 4) EPP patients (n = 19). This polymorphic variant responded to the Hardy-Weinberg equilibrium law in the studied groups. The allele frequency of nc.-582 A > G for variant G was: 0.101 in the control group; 0.189 for PCT; 0.154 and 0.147 in HH with and without mutations in HFE respectively; 0.158 in EPP. Statistical analyses were performed using VCC-STAT software. Differences between values were considered significant when p < 0.05. Significant differences between the control and analized groups were not observed, indicating that in Argentina, PCT triggering would not be associated to this genetic variant.