Genetic variation in the ABCA1 gene,HDL cholesterol,and risk of ischemic heart disease in the general population |
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| Authors: | Ruth Frikke-Schmidt |
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| Affiliation: | 1. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;2. Michael E. DeBakey Veterans Administration Medical Center and Baylor College of Medicine, Houston, Texas, USA;3. Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA;4. Department of Medicine, Division of Nephrology, University of Illinois, Chicago, Illinois, USA;5. Center for Hypertension, Kidney & Vascular Research, Georgetown University Medical Center, Washington, DC, USA;6. Department of Medicine, MetroHealth Medical Center and Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA;7. Internal Medicine, Renal Section, New Mexico Veterans Administration Health Care System, Albuquerque, New Mexico, USA;8. National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, Maryland, USA;9. Department of Nephrology, University of Tennessee Health Science Center and Veterans Affairs Medical Center, Memphis, Tennessee, USA;10. Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;1. Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;2. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;3. Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;1. Department of Surgery, Washington University School of Medicine, St. Louis, Missouri;2. Department of Thoracic Surgery, Sapienza University, Rome, Italy;3. Departments of Anesthesia;4. Medicine;5. Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri;6. APT Therapeutics Inc, St. Louis, Missouri;1. Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;2. Department of Cardiology, Westmead Hospital, Westmead, NSW, Australia;3. Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia;4. Department of Clinical Haematology, Westmead Hospital, Westmead, NSW, Australia;5. National Amyloidosis Centre, University College Medical School, London, United Kingdom |
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| Abstract: | Epidemiological studies consistently demonstrate a strong inverse association between low levels of high-density lipoprotein (HDL) cholesterol and increased risk of ischemic heart disease (IHD). This review focuses on whether both rare and common genetic variation in ABCA1 contributes to plasma levels of HDL cholesterol and to risk of IHD in the general population, and further seeks to understand whether low levels of HDL cholesterol per se are causally related to IHD. Studies of the ABCA1 gene demonstrate a general strategy for detecting functional genetic variants, and show that both common and rare ABCA1 variants contribute to levels of HDL cholesterol and risk of IHD in the general population. The association between ABCA1 variants and risk of IHD appears, however, to be independent of plasma levels of HDL cholesterol. With the recent identification of the largest number of individuals heterozygous for loss-of-function mutations in ABCA1 worldwide, population studies suggests that genetically low HDL cholesterol per se does not predict an increased risk of IHD, and thus questions the causality of isolated low levels of HDL cholesterol for the development of IHD. |
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