Genetic variation at the proprotein convertase subtilisin/kexin type 5 gene modulates high-density lipoprotein cholesterol levels

Circulation: Cardiovascular Genetics

Volumn 2, Issue 5, 2009, Pages 467-475

  Iatan, Iulia ^a   Dastani, Zari ^a   Do, Ron ^a   Weissglas Volkov, Daphna ^b   Ruel, Isabelle ^a   Lee, Jenny C ^b   Huertas Vazquez, Adriana ^b   Taskinen, Marja Riitta ^c   Prat, Annik ^d   Seidah, Nabil G ^d   Pajukanta, Päivi ^b   Engert, James C ^a   Genest, Jacques ^a  

^a ROYAL VICTORIA HOSPITAL   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF HELSINKI   (Finland)

^d CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

Author keywords

Cholesterol; Coronary disease; Genetics; Lipids; Lipoproteins

Indexed keywords

APOLIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; KEXIN; SERINE PROTEINASE; SUBTILISIN; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; VERY LOW DENSITY LIPOPROTEIN; PROPROTEIN CONVERTASE 5;

ADULT; ARTICLE; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CORONARY ARTERY DISEASE; ENZYME ACTIVATION; ENZYME ACTIVITY; FAMILY STUDY; FEMALE; GENE; GENE LOCUS; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HUMAN; LIPOPROTEIN BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; PCSK5 GENE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; AGED; BLOOD; CASE CONTROL STUDY; CAUCASIAN; GENETICS; MIDDLE AGED; PEDIGREE;

ADULT; AGED; CASE-CONTROL STUDIES; CHOLESTEROL, HDL; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENETIC VARIATION; GENOTYPE; HUMANS; MALE; MIDDLE AGED; PEDIGREE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROPROTEIN CONVERTASE 5;

EID: 77949429060     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.109.877811     Document Type: Article

References (38)

1. Iatan I, Alrasadi K, Ruel I, Alwaili K, Genest J. Effect of ABCA1 mutations on risk for myocardial infarction. Curr Atheroscler Rep. 2008; 10:413-426.
2. Dastani Z, Engert JC, Genest J, Marcil M. Genetics of high-density lipoproteins. Curr Opin Cardiol. 2006;21:329-335.
3. Hassan HH, Bailey D, Lee DY, Iatan I, Hafiane A, Ruel I, Krimbou L, Genest J. Quantitative analysis of ABCA1-dependent compartmentalization and trafficking of apolipoprotein A-I: implications for determining cellular kinetics of nascent high density lipoprotein biogenesis. J Biol Chem. 2008;283:11164-11175.
4. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res. 2005;96:1221-1232.
5. Jaye M, Lynch KJ, Krawiec J, Marchadier D, Maugeais C, Doan K, South V, Amin D, Perrone M, Rader DJ. A novel endothelial-derived lipase that modulates HDL metabolism. Nat Genet. 1999;21:424-428.
6. Shimamura M, Matsuda M, Yasumo H, Okazaki M, Fujimoto K, Kono K, Shimizugawa T, Ando Y, Koishi R, Kohama T, Sakai N, Kotani K, Komuro R, Ishida T, Hirata K, Yamashita S, Furukawa H, Shimomura I. Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase. Arterioscler Thromb Vasc Biol. 2007; 27:366-372.
7. Jin W, Wang X, Millar JS, Quertermous T, Rothblat GH, Glick JM, Rader DJ. Hepatic proprotein convertases modulate HDL metabolism. Cell Metab. 2007;6:129-136.
8. Seidah NG, Khatib AM, Prat A. The proprotein convertases and their implication in sterol and/or lipid metabolism. Biol Chem. 2006;387: 871-877.
9. Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci USA. 2004;101:7100-7105.
10. Lusson J, Vieau D, Hamelin J, Day R, Chretien M, Seidah NG. cDNA structure of the mouse and rat subtilisin/kexin-like PC5: a candidate proprotein convertase expressed in endocrine and nonendocrine cells. Proc Natl Acad Sci USA. 1993;90:6691-6695.
11. Nour N, Mayer G, Mort JS, Salvas A, Mbikay M, Morrison CJ, Overall CM, Seidah NG. The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases. Mol Biol Cell. 2005;16:5215-5226.
12. Essalmani R, Zaid A, Marcinkiewicz J, Chamberland A, Pasquato A, Seidah NG, Prat A. In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate. Proc Natl Acad Sci USA. 2008;105:5750-5755.
13. Essalmani R, Hamelin J, Marcinkiewicz J, Chamberland A, Mbikay M, Chretien M, Seidah NG, Prat A. Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse. Mol Cell Biol. 2006;26:354-361.
14. Miranda L, Wolf J, Pichuantes S, Duke R, Franzusoff A. Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ T lymphocytes. Proc Natl Acad Sci USA. 1996;93: 7695-7700.
15. Nakagawa T, Hosaka M, Torii S, Watanabe T, Murakami K, Nakayama K. Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4. J Biochem. 1993;113:132-135.
16. Falchi M, Andrew T, Snieder H, Swaminathan R, Surdulescu GL, Spector TD. Identification of QTLs for serum lipid levels in a female sib-pair cohort: a novel application to improve the power of two-locus linkage analysis. Hum Mol Genet. 2005;14:2971-2979.
17. Department of health and human services, Public Health Service. NIH Washington DC Lipid Research Clinics Population Studies Databook. Washington DC: NIH Publication; 1980;80-1527.
18. Weber M, McNicoll S, Marcil M, Connelly P, Lussier-Cacan S, Davignon J, Latour Y, Genest J Jr. Metabolic factors clustering, lipoprotein cholesterol, apolipoprotein B, lipoprotein (a) and apolipoprotein E phenotypes in premature coronary artery disease in French Canadians. Can J Cardiol. 1997;13:253-260.
19. Alrasadi K, Ruel IL, Marcil M, Genest J. Functional mutations of the ABCA1 gene in subjects of French-Canadian descent with HDL deficiency. Atherosclerosis. 2006;188:281-291.
20. Marcil M, Yu L, Krimbou L, Boucher B, Oram JF, Cohn JS, Genest J Jr. Cellular cholesterol transport and efflux in fibroblasts are abnormal in subjects with familial HDL deficiency. Arterioscler Thromb Vasc Biol. 1999;19:159-169.
21. Pajukanta P, Allayee H, Krass KL, Kuraishy A, Soro A, Lilja HE, Mar R, Taskinen MR, Nuotio I, Laakso M, Rotter JI, de Bruin TW, Cantor RM, Lusis AJ, Peltonen L. Combined analysis of genome scans of dutch and finnish families reveals a susceptibility locus for highdensity lipoprotein cholesterol on chromosome 16q. Am J Hum Genet. 2003;72:903-917.
22. Pajukanta P, Nuotio I, Terwilliger JD, Porkka KV, Ylitalo K, Pihlajamaki J, Suomalainen AJ, Syvanen AC, Lehtimaki T, Viikari JS, Laakso M, Taskinen MR, Ehnholm C, Peltonen L. Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23. Nat Genet. 1998;18: 369-373. (Pubitemid 28158167)
23. Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000;132:365-386.
24. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21: 263-265.
25. Ehrich M, Bocker S, van den BD. Multiplexed discovery of sequence polymorphisms using base-specific cleavage and MALDI-TOF MS. Nucleic Acids Res. 2005;33:e38.
26. O'Connell JR, Weeks DE. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998; 63:259-266.
27. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559-575.
28. Tu IP, Balise RR, Whittemore AS. Detection of disease genes by use of family data. II. Application to nuclear families. Am J Hum Genet. 2000; 66:1341-1350.
29. Abecasis GR, Cardon LR, Cookson WO. A general test of association for quantitative traits in nuclear families. Am J Hum Genet. 2000;66: 279-292.
30. Havill LM, Dyer TD, Richardson DK, Mahaney MC, Blangero J. The quantitative trait linkage disequilibrium test: a more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification. BMC Genet. 2005;6(suppl 1):S91.
31. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet. 2006;38:209-213.
32. Seidah NG, Prat A. The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med. 2007;85:685-696.
33. Broedl UC, Jin W, Rader DJ. Endothelial lipase: a modulator of lipoprotein metabolism upregulated by inflammation. Trends Cardiovasc Med. 2004;14:202-206.
34. Yancey PG, Kawashiri MA, Moore R, Glick JM, Williams DL, Connelly MA, Rader DJ, Rothblat GH. In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol efflux. J Lipid Res. 2004;45:337-346.
35. Koishi R, Ando Y, Ono M, Shimamura M, Yasumo H, Fujiwara T, Horikoshi H, Furukawa H. Angptl3 regulates lipid metabolism in mice. Nat Genet. 2002;30:151-157.
36. Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K, Inaba T, Minekura H, Kohama T, Furukawa H. ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase. J Biol Chem. 2002;277:33742-33748.
37. Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, Roos C, Hirschhorn JN, Berglund G, Hedblad B, Groop L, Altshuler DM, Newton-Cheh C, Orho-Melander M. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358: 1240-1249.
38. Cao H, Mok A, Miskie B, Hegele RA. Single-nucleotide polymorphisms of the proprotein convertase subtilisin/kexin type 5 (PCSK5) gene. J Hum Genet. 2001;46:730-732