Hereditary hemochromatosis is a disorder of iron metabolism that leads to iron overload and can progress to fatal complications such as terminal hepatic failure, primary hepatocellular carcinoma, and congestive heart failure. Gene mutations have been identified that are associated with hemochromatosis, although many individuals with these mutations do not display signs of hemochromatosis. Therefore, it is important to determine factors interacting with these genes that are associated with hemochromatosis outcomes. Telomere length is a novel biomarker that represents biological aging. It is unclear how hemochromatosis genes and iron overload relates to telomere length.
The aims of the study are to 1) Determine the relationship between leukocyte telomere length and hemochromatosis related outcomes, 2) Examine the relationship between telomere length and genotype and phenotype indicators for hemochromatosis, and 3) Analyze the impact of lifestyle and clinical care on telomere length and hemochromatosis outcomes. We propose to conduct an analysis of the Hemochromatosis and Iron Overload Screening (HEIRS) Study public use data set. We will conduct new analyses of telomere length from stored samples and merge that with other existing data from this study. During this two-year project, we will examine the impact of treatment and lifestyle variables on telomere length and hemochromatosis related outcomes among these individuals to see which variables act as buffers to aging and morbidity risk. We will study 4 groups included in the HEIRS Study Comprehensive Clinical Exam which will allow us to examine both the impact of hemochromatosis genotype and phenotypic expression of iron overload. The first group will be individuals who are HFE gene positive and are phenotype positive for elevated iron (elevated serum ferritin (SF) and elevated transferring saturation (TS)). The second group will be individuals who are HFE gene negative and are phenotype positive. The third group will be individuals who are HFE gene positive and are phenotype negative for elevated iron. The final group will be individuals who are HFE gene negative and are phenotype negative for elevated iron. The total number of subjects to be studied will be 1,157. Although there is an increased risk of development of a variety of clinical conditions in patients with HH, it is not known whether HH is associated with leukocyte telomere length and whether certain treatment and lifestyle activities can buffer the relationship. This study is innovative in that the cumulative stress and heritable predispositions for disease are represented in telomere length. This study will extend previous knowledge of accelerated aging and morbidity among individuals with hemochromatosis and iron overload by examining factors that may accelerate or slow the biological aging process and corresponding development of disease. This project has potential implications for early detection and screening using phenotypic markers as well as compliance with treatment and a healthy lifestyle.

Public Health Relevance

Hereditary hemochromatosis is a common disorder of iron metabolism that leads to iron overload and canprogress to fatal complications such as terminal hepatic failure; primary hepatocellular carcinoma; andintractable congestive heart failure. Telomere length is a novel biomarker that represents biological aging; it isunclear how hemochromatosis genes and iron overload relates to telomere length. This project is an attemptto understand accelerated aging and morbidity among individuals with hemochromatosis and iron overload byexamining factors that may accelerate or slow the biological aging process and corresponding development ofdisease.

Agency
National Institute of Health (NIH)
Institute
Centers for Disease Control and Prevention (NCBDD)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DD000754-03S1
Application #
8792891
Study Section
Special Emphasis Panel (ZDD1-MED (03))
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
Fiscal Year
2013
Total Cost
$36,816
Indirect Cost
$12,094
Name
University of Florida
Department
Type
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Mainous 3rd, Arch G; Tanner, Rebecca J; Hulihan, Mary M et al. (2014) The impact of chelation therapy on survival in transfusional iron overload: a meta-analysis of myelodysplastic syndrome. Br J Haematol 167:720-3
Mainous 3rd, Arch G; Wright, Robert U; Hulihan, Mary M et al. (2013) Telomere length and elevated iron: the influence of phenotype and HFE genotype. Am J Hematol 88:492-6
Mainous 3rd, Arch G; Johnson, Sharleen P; Chirina, Svetlana et al. (2013) Academic family physicians' perception of genetic testing and integration into practice: a CERA study. Fam Med 45:257-62
Mainous 3rd, Arch G; Weinberg, Eugene D; Diaz, Vanessa A et al. (2012) Calcium channel blocker use and serum ferritin in adults with hypertension. Biometals 25:563-8