This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Background: Porphyria cutanea tarda (PCT) develops in some individuals who are predisposed by certain environmental and inherited susceptibility factors, and is manifested by skin photosensitivity and liver damage. Susceptibility factors include hepatitis C, alcohol use, smoking, iron overload, HIV, estrogens and an inherited partial deficiency of UROD. Why PCT develops in only a few individuals with these susceptibility factors, many of which are relatively common, is not known, and additional influences - most likely additional inherited differences - remain to be identified. Hypothesis: We will investigate the novel hypothesis that genetic differences in enzymes that metabolize foreign chemicals may contribute to developing PCT.
Specific Aims and Procedures (summary):
Aim 1. At least 120 patients with well documented PCT will be enrolled in a case-control study that will include two different groups of matched controls. DNA and lymphocytes will be isolated, and patients and controls studied for specific genetic differences in specific enzymes (e.g.CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1).
Aim 2. Associations with clinical features, known susceptibility factors, treatment response and frequency of relapse will be examined using logistic regression models.
Aim 3. DNA and lymphocytes from these patients and matched controls, and information regarding clinical features and known susceptibility factors will be stored as a resource for future studies of additional genetic susceptibility factors for PCT.Experimental Design (summary): Laboratory methods are established in our laboratories. Results will be summarized and analyzed statistically to compare the PCT group with the two control groups. Part of the analyses pertain to the PCT cases only, as the variables under investigation are those found only among the cases, and will include consideration of factors that are associated with treatment response and relapse after treatment. Significance (summary): This study and projects which follow will lead to a better understanding of PCT and also contribute to knowledge about how agents such as alcohol and hepatitis C interact with genetic factors in causing human liver diseases.
|Gelman, Benjamin B; Endsley, Janice; Kolson, Dennis (2018) When do models of NeuroAIDS faithfully imitate ""the real thing""? J Neurovirol 24:146-155|
|Mourtakos, S P; Tambalis, K D; Panagiotakos, D B et al. (2017) Association between gestational weight gain and risk of obesity in preadolescence: a longitudinal study (1997-2007) of 5125 children in Greece. J Hum Nutr Diet 30:51-58|
|Ramanujam, V-M S; Nayeem, Fatima; Anderson, Karl E et al. (2017) Riboflavin as an independent and accurate biomarker for adherence in a randomized double-blind and placebo-controlled clinical trial. Biomarkers 22:508-516|
|Laffer, Cheryl L; Scott 3rd, Robert C; Titze, Jens M et al. (2016) Hemodynamics and Salt-and-Water Balance Link Sodium Storage and Vascular Dysfunction in Salt-Sensitive Subjects. Hypertension 68:195-203|
|Hosoki, Koa; Ying, Sun; Corrigan, Christopher et al. (2015) Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1. PLoS One 10:e0126035|
|Murai, Hiroki; Okazaki, Shintaro; Hayashi, Hisako et al. (2015) Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells. Biochem Biophys Res Commun 464:969-974|
|Diaz, Eva C; Herndon, David N; Porter, Craig et al. (2015) Effects of pharmacological interventions on muscle protein synthesis and breakdown in recovery from burns. Burns 41:649-57|
|Tuvdendorj, Demidmaa; Chinkes, David L; Bahadorani, John et al. (2014) Comparison of bolus injection and constant infusion methods for measuring muscle protein fractional synthesis rate in humans. Metabolism 63:1562-7|
|Sallam, Hanaa S; McNearney, Terry A; Chen, Jiande D Z (2014) Acupuncture-based modalities: novel alternative approaches in the treatment of gastrointestinal dysmotility in patients with systemic sclerosis. Explore (NY) 10:44-52|
|Petersen, John R; Stevenson, Heather L; Kasturi, Krishna S et al. (2014) Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C. J Clin Gastroenterol 48:370-6|
Showing the most recent 10 out of 465 publications