These investigators have ascertained one of the largest collection of pedigrees with hereditary iron overload. Over 300 families have been ascertained. Extensive phenotypic analyses have been completed and genotyping studies have demonstrated that approximately 90% of the pedigrees have iron overload associated with homozygosity for the cysteine 282 tyrosine mutation of the HFE gene. The current focus is to test the hypothesis that hemochromatosis is a disease caused by malregulated cellular iron export. Epstein-Barr Virus (EBV) transformed lymphocytes have been generated from at least one member of every pedigree and an in vitro system has been devised to analyze cellular iron export. The human macrophage model of regulated iron export (based on animal models of genetic iron overload) is also being developed utilizing macrophages isolated from bone marrow aspirations of patients with hemochromatosis associated with the ancestral HFE mutation and those with other mutations of the HFE locus or no HFE associated mutations. These in vitro cell culture models are in developmental state at the present. A large clinical phenotyping study has been completed and demonstrated that approximately half of the patients with hemochromatosis developed disease related morbidity. A manuscript has been submitted describing this study and provided ample documentation that morbidity is a common consequence of homozygosity for hemochromatosis gene mutations, thus justifying large-scale population screening studies.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
3M01RR000064-35S1
Application #
6218401
Study Section
Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
35
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Adams, Ted D; Davidson, Lance E; Litwin, Sheldon E et al. (2017) Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med 377:1143-1155
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Archer, Stephanie Wilson; Carlo, Waldemar A; Truog, William E et al. (2016) Improving publication rates in a collaborative clinical trials research network. Semin Perinatol 40:410-417
Phelps, Dale L; Ward, Robert M; Williams, Rick L et al. (2016) Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 80:209-17
Harper, Lorie M; Mele, Lisa; Landon, Mark B et al. (2016) Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes. Obstet Gynecol 127:893-8
Bowles, Neil E; Jou, Chuanchau J; Arrington, Cammon B et al. (2015) Exome analysis of a family with Wolff-Parkinson-White syndrome identifies a novel disease locus. Am J Med Genet A 167A:2975-84
Priester, Tiffany; Ault, Travis G; Davidson, Lance et al. (2015) Coronary calcium scores 6 years after bariatric surgery. Obes Surg 25:90-6
Adams, T D; Hammoud, A O; Davidson, L E et al. (2015) Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery. Int J Obes (Lond) 39:686-94

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