PURPOSE OF REVIEW: To review gene regulation of HDL-cholesterol and discuss molecular abnormalities in HDL candidate genes that may lead to human pathologic states. RECENT FINDINGS: The inverse association between HDL-cholesterol and vascular disease, especially coronary heart disease, has long been recognized, but understanding gene regulation of HDL in humans gained considerable momentum following the identification of ABCA1 as playing a pivotal role in reverse cholesterol transport. Recent data suggest that potentially important targets for upregulating HDL in humans include upregulators of ABCA1 and APOA1 (e.g. peroxisome proliferator activated receptor and liver X receptor agonists) and downregulators of CETP (e.g. JTT-705). A host of other nuclear receptors under investigation in animal models may advance to human testing in the near future. SUMMARY: Disorders affecting HDL metabolism are complex because monogenic disorders causing low HDL do not necessarily correlate with premature vascular disease. To date, pathologic phenotypes have only been deduced among several HDL candidate genes. Understanding the genetic underpinnings associated with variant HDL and reverse cholesterol transport provides an exceptional opportunity to identify novel agents that may optimize this process and reduce vascular event rates beyond currently available LDL lowering therapies.
PURPOSE OF REVIEW: To review gene regulation of HDL-cholesterol and discuss molecular abnormalities in HDL candidate genes that may lead to human pathologic states. RECENT FINDINGS: The inverse association between HDL-cholesterol and vascular disease, especially coronary heart disease, has long been recognized, but understanding gene regulation of HDL in humans gained considerable momentum following the identification of ABCA1 as playing a pivotal role in reverse cholesterol transport. Recent data suggest that potentially important targets for upregulating HDL in humans include upregulators of ABCA1 and APOA1 (e.g. peroxisome proliferator activated receptor and liver X receptor agonists) and downregulators of CETP (e.g. JTT-705). A host of other nuclear receptors under investigation in animal models may advance to human testing in the near future. SUMMARY: Disorders affecting HDL metabolism are complex because monogenic disorders causing low HDL do not necessarily correlate with premature vascular disease. To date, pathologic phenotypes have only been deduced among several HDL candidate genes. Understanding the genetic underpinnings associated with variant HDL and reverse cholesterol transport provides an exceptional opportunity to identify novel agents that may optimize this process and reduce vascular event rates beyond currently available LDL lowering therapies.
Authors: Sean A Wiltshire; Eduardo Diez; Qianqian Miao; Marie-Pierre Dubé; Mireille Gagné; Olivier Paquette; Ronald G Lafrenière; Momar Ndao; Lawrence W Castellani; Emil Skamene; Silvia M Vidal; Anny Fortin Journal: Physiol Genomics Date: 2012-07-17 Impact factor: 3.107
Authors: Jenny C Lee; Daphna Weissglas-Volkov; Mira Kyttälä; Zari Dastani; Rita M Cantor; Eric M Sobel; Christopher L Plaisier; James C Engert; Marleen M J van Greevenbroek; John P Kane; Mary J Malloy; Clive R Pullinger; Adriana Huertas-Vazquez; Carlos A Aguilar-Salinas; Teresa Tusie-Luna; Tjerk W A de Bruin; Bradley E Aouizerat; Carla C J van der Kallen; Carlo M Croce; Rami I Aqeilan; Michel Marcil; Jorma S A Viikari; Terho Lehtimäki; Olli T Raitakari; Johanna Kuusisto; Markku Laakso; Marja-Riitta Taskinen; Jacques Genest; Päivi Pajukanta Journal: Am J Hum Genet Date: 2008-08 Impact factor: 11.025