Genomes and Genes
GENETIC EPIDEMIOLOGY OF AGING IN UTAH PEDIGREES
Principal Investigator: Steven Hunt
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
- Strategies to improve detection of hypertension genesSteven C Hunt
Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA
J Nutrigenet Nutrigenomics 3:182-91. 2010..Genes found to be significant in such studies should be densely typed in clinical trials and large population studies to assess public health and clinical applications of the findings...
- Vitamin D dependent effects of APOA5 polymorphisms on HDL cholesterolBrian H Shirts
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Atherosclerosis 222:167-74. 2012..Vitamin D and serum lipid levels are risk factors for cardiovascular disease. We sought to determine if vitamin D (25OHD) interacts at established lipid loci potentially explaining additional variance in lipids...
- Effects of ethanol intake on lipoproteinsEliot A Brinton
Utah Foundation for Biomedical Research, Salt Lake City, UT, USA
Curr Atheroscler Rep 14:108-14. 2012..Application of these findings in clinical practice remains problematic, however, due to the lack of randomized, controlled clinical trials of ethanol and due to the potential hazards of ethanol consumption...
- The epithelial sodium channel γ-subunit gene and blood pressure: family based association, renal gene expression, and physiological analysesCara J Büsst
Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia
Hypertension 58:1073-8. 2011..07) 1.7-fold higher expression of SCNN1G compared with normotensive controls. These data provide genetic and phenotypic evidence in support of a role for a common genetic variant of SCNN1G in blood pressure determination...
- Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCRAbraham Aviv
The Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
Nucleic Acids Res 39:e134. 2011..We discuss the ramifications of these findings with regard to measurements of telomere length/DNA content in epidemiological/clinical circumstances...
- Meta-analysis of genome-wide linkage scans for renal function traitsMadhumathi Rao
Division of Nephrology, Tufts Medical Center, Boston, MA, USA
Nephrol Dial Transplant 27:647-56. 2012..Genome scan meta-analysis (GSMA) is a quantitative method to synthesize linkage results from independent studies and assess their concordance...
- Evaluation of the gene-age interactions in HDL cholesterol, LDL cholesterol, and triglyceride levels: the impact of the SORT1 polymorphism on LDL cholesterol levels is age dependentBrian H Shirts
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
Atherosclerosis 217:139-41. 2011..These findings may help elucidate the mode of action of the SORT1 gene and impact potential therapeutic interventions targeting this pathway...
- Effects of ethanol intake on lipoproteins and atherosclerosisEliot A Brinton
Department of Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA
Curr Opin Lipidol 21:346-51. 2010..This article reviews published studies regarding effects of ethanol intake on lipoprotein levels and function as they relate to atherosclerosis, with special emphasis on recent publications in the past 2 years...
- Genetic architecture of complex traits predisposing to nephropathy: hypertensionSteven C Hunt
Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84108, USA
Semin Nephrol 30:150-63. 2010..A brief review is provided of some key genes found to be associated with hypertension, including the genes identified from the nine genome-wide association studies published to date...
- Two-dimensional, sex-specific autosomal linkage scan of the number of sodium pump sitesSandra J Hasstedt
Department of Human Genetics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah 84112, USA
J Hypertens 28:740-7. 2010..Obesity, hypertension, and diabetes associate with the activity of the sodium pump, motivating gene discovery for sodium pump number...
- Altered composition of triglyceride-rich lipoproteins and coronary artery disease in a large case-control studyPaul 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...
- Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery diseaseArno 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...
- Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressuresSteven 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...
- Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglyceridesHilary 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...