GENETIC EPIDEMIOLOGY OF AGING IN UTAH PEDIGREES

Summary

Principal Investigator: Steven Hunt
Affiliation: University of Utah
Country: USA
Abstract: DESCRIPTION: (provided by applicant) One aspect of aging that leads to the most common forms of morbidity and mortality is the aging of the vascular system. One of the most important processes involves the balance between the oxidative burden seen by the vasculature and the capacity of antioxidants to counteract that burden. Telomere length is also closely related to vascular aging, measuring biological age rather than chronological age. Telomeres determine processes related to cellular and DNA repair, cellular replicative capacity, and apoptosis. Shorter telomeres have been associated with decreased longevity and increased pulse pressure and cardiovascular disease. In addition, oxidant/antioxidant balance appears to play an important role in regulating the length of telomeres. Although the individual effects of each system have been studied in vitro and in small samples of human subjects, their individual and interactive effects have not been studied in large population cohorts to assess their influence on vascular aging and morbidity. One of the aims of this grant is to relate these two systems to comprehensive measures of vascular dysfunction and aging in a 22-year longitudinally followed cohort of 1500 relatives in 98 large Utah pedigrees. These comprehensive measures assess aging in multiple vascular beds and include small and large artery stiffness/compliance, carotid intima-media thickness, coronary and abdominal aortic calcium levels, endothelial function (flow mediated dilation), peripheral artery disease, and pulse pressure. Multiple measures of baseline and 22-year rates of change in total antioxidant capacity, indicators of total oxidant stress, and telomere length will be related to these subclinical aging indicators. Because pedigrees are being studied which already have genome search markers genotyped, some of the underlying genes contributing to the expression of the above phenotypes may be localized by linkage and identified through pedigree-based haplotype association analyses. Evidence of significant linkage for multiple antioxidants and other indicators of aging have been found in these pedigrees, and the underlying genes will be pursued and related to the subclinical vascular measures. This collection of longitudinally followed pedigrees provides a powerful study design to address a wide range of genetic epidemiological analyses of aging.
Funding Period: 2000-09-30 - 2009-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides
    Hilary Coon
    Neurodevelopmental Genetics Project, Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA
    Hum Genet 117:444-51. 2005
  2. ncbi Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressures
    Steven C Hunt
    Cardiovascular Genetics Division, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA
    Hypertension 47:532-6. 2006
  3. ncbi Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease
    Arno Lingenhel
    Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schopfstrasse 41, A 6020 Innsbruck, Austria
    Exp Gerontol 43:1102-7. 2008
  4. ncbi Altered composition of triglyceride-rich lipoproteins and coronary artery disease in a large case-control study
    Paul N Hopkins
    Cardiovascular Genetics Research, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT 84108, USA
    Atherosclerosis 207:559-66. 2009

Scientific Experts

Detail Information

Publications4

  1. ncbi Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides
    Hilary Coon
    Neurodevelopmental Genetics Project, Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA
    Hum Genet 117:444-51. 2005
    ..This study replicates the involvement of USF1 in FCHL and related lipid traits in a family sample not ascertained for FCHL...
  2. ncbi Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressures
    Steven C Hunt
    Cardiovascular Genetics Division, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA
    Hypertension 47:532-6. 2006
    ..These results additionally confirm the involvement of SLC4A5 with blood pressure control, although the mechanism is still unclear...
  3. ncbi Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease
    Arno Lingenhel
    Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schopfstrasse 41, A 6020 Innsbruck, Austria
    Exp Gerontol 43:1102-7. 2008
    ..1mg/dl increase of bilirubin. These results indicate that it is rather decreased bilirubin levels in general than the changes in the genetic variation of this gene that increase the risk for CAD...
  4. ncbi Altered composition of triglyceride-rich lipoproteins and coronary artery disease in a large case-control study
    Paul N Hopkins
    Cardiovascular Genetics Research, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT 84108, USA
    Atherosclerosis 207:559-66. 2009
    ..30 with TG>150mg/dL) indicative of atherogenic remnant accumulation (type III hyperlipidemia). However, virtually no reports are available which examine potential associations between CAD and VLDL-C/TG at the lower end of the spectrum...