Evidence for several independent genetic variants affecting lipoprotein (a) cholesterol levels

Human Molecular Genetics

Volumn 24, Issue 8, 2015, Pages 2390-2400

  Lu, Wensheng ^a,b   Cheng, Yu Ching ^a,c   Chen, Keping ^a   Wang, Hong ^a   Gerhard, Glenn S ^d,e   Still, Christopher D ^d   Chu, Xin ^d   Yang, Rongze ^a   Parihar, Ankita ^a   O'Connell, Jeffrey R ^a   Pollin, Toni I ^a   Angles Cano, Eduardo ^f,g   Quon, Michael J ^a   Mitchell, Braxton D ^a   Shuldiner, Alan R ^a,c   Fu, Mao ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b PEOPLE'S HOSPITAL OF GUANGXI ZHUANG AUTONOMOUS REGION   (China)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

^d GEISINGER MEDICAL CENTER   (United States)

^e PENN STATE COLLEGE OF MEDICINE   (United States)

^f INSERM   (France)

^g UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN A4; APOLIPOPROTEIN A5; APOLIPOPROTEIN C3; CHOLESTEROL; LIPOPROTEIN A; MESSENGER RNA;

ADULT; ARTICLE; CHROMOSOME; CHROMOSOME 11Q23; CHROMOSOME 6Q; CHROMOSOME 6Q25-26; FEMALE; GENE CLUSTER; GENE CONTROL; GENE LOCUS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HETEROZYGOTE; HUMAN; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; REGULATORY MECHANISM; SINGLE NUCLEOTIDE POLYMORPHISM; AGED; ATHEROSCLEROSIS; CHEMISTRY; CHROMOSOME 6; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; KRINGLE DOMAIN; METABOLISM; MIDDLE AGED;

ADULT; AGED; ATHEROSCLEROSIS; CHOLESTEROL; CHROMOSOMES, HUMAN, PAIR 6; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; KRINGLES; LIPOPROTEIN(A); MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84926500499     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddu731     Document Type: Article

References (54)

1. (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA, 285, 2486-2497.
2. Kamstrup, P.R., Tybjaerg-Hansen, A., Steffensen, R. and Nordestgaard, B.G. (2009) Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA, 301, 2331-2339.
3. Clarke, R., Peden, J.F., Hopewell, J.C., Kyriakou, T., Goel, A., Heath, S.C., Parish, S., Barlera, S., Franzosi, M.G., Rust, S. et al. (2009) Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl. J. Med., 361, 2518-2528.
4. Tregouet, D.A., Konig, I.R., Erdmann, J., Munteanu, A., Braund, P.S., Hall, A.S., Grosshennig, A., Linsel-Nitschke, P., Perret, C., DeSuremain, M. et al. (2009) Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat. Genet., 41, 283-285.
5. Haberland, M.E., Fless, G.M., Scanu, A.M. and Fogelman, A.M. (1992) Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages. J. Biol. Chem., 267, 4143-4151.
6. Longenecker, J.C., Klag, M.J., Marcovina, S.M., Powe, N.R., Fink, N.E., Giaculli, F. and Coresh, J. (2002) Small apolipoprotein(a) size predicts mortality in end-stage renal disease: The CHOICE study. Circulation, 106, 2812-2818.
7. Grainger, D.J., Kirschenlohr, H.L., Metcalfe, J.C., Weissberg, P.L., Wade, D.P. and Lawn, R.M. (1993) Proliferation of human smooth muscle cells promoted by lipoprotein(a). Science, 260, 1655-1658.
8. Enas, E.A., Chacko, V., Senthilkumar, A., Puthumana, N. and Mohan, V. (2006) Elevated lipoprotein(a)-a genetic risk factor for premature vascular disease in people with and without standard risk factors: a review. Dis. Mon., 52, 5-50.
9. Caplice, N.M., Panetta, C., Peterson, T.E., Kleppe, L.S., Mueske, C.S., Kostner, G.M., Broze, Jr. G.J. and Simari, R.D. (2001) Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood, 98, 2980-2987.
10. Marcovina, S.M. and Koschinsky, M.L. (2003) Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedside. Curr. Opin. Lipidol., 14, 361-366.
11. McLean, J.W., Tomlinson, J.E., Kuang, W.J., Eaton, D.L., Chen, E.Y., Fless, G.M., Scanu, A.M. and Lawn, R.M. (1987) cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature, 330, 132-137.
12. Ober, C., Abney, M. and McPeek, M.S. (2001) The genetic dissection of complex traits in a founder population. Am. J. Hum. Genet., 69, 1068-1079.
13. Rainwater, D.L., Kammerer, C.M., VandeBerg, J.L. and Hixson, J.E. (1997) Characterization of the genetic elements controlling lipoprotein(a) concentrations in Mexican Americans. Evidence for at least three controlling elements linked to LPA, the locus encoding apolipoprotein(a). Atherosclerosis, 128, 223-233.
14. Kraft, H.G., Kochl, S., Menzel, H.J., Sandholzer, C. and Utermann, G. (1992) The apolipoprotein (a) gene: a transcribed hypervariable locus controlling plasma lipoprotein (a) concentration. Hum. Genet., 90, 220-230.
15. Hasstedt, S.J., Wilson, D.E., Edwards, C.Q., Cannon, W.N., Carmelli, D. and Williams, R.R. (1983) The genetics of quantitative plasma Lp(a): analysis of a large pedigree. Am. J. Med. Genet., 16, 179-188.
16. Morton, N.E., Berg, K., Dahlen, G., Ferrell, R.E. and Rhoads, G.G. (1985) Genetics of the Lp lipoprotein in Japanese-Americans. Genet. Epidemiol., 2, 113-121.
17. Hasstedt, S.J. and Williams, R.R. (1986) Three alleles for quantitative Lp(a). Genet. Epidemiol., 3, 53-55.
18. Rosby, O. and Berg, K. (2000) LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level. J. Intern. Med., 247, 139-152.
19. Ogorelkova, M., Kraft, H.G., Ehnholm, C. and Utermann, G. (2001) Single nucleotide polymorphisms in exons of the apo (a) kringles IV types 6 to 10 domain affect Lp(a) plasma concentrations and have different patterns in Africans and Caucasians. Hum. Mol. Genet., 10, 815-824.
20. Lim, E.T., Wurtz, P., Havulinna, A.S., Palta, P., Tukiainen, T., Rehnstrom, K., Esko, T., Magi, R., Inouye, M., Lappalainen, T. et al. (2014) Distribution and medical impact of loss-offunction variants in the Finnish founder population. PLoS Genet., 10, e1004494.
21. Lopez, S., Buil, A., Ordonez, J., Souto, J.C., Almasy, L., Lathrop, M., Blangero, J., Blanco-Vaca, F., Fontcuberta, J. and Soria, J.M. (2008) Genome-wide linkage analysis for identifying quantitative trait loci involved in the regulation of lipoprotein a (Lpa) levels. Eur. J. Hum. Genet., 16, 1372-1379.
22. Barlera, S., Specchia, C., Farrall, M., Chiodini, B.D., Franzosi, M.G., Rust, S., Green, F., Nicolis, E.B., Peden, J., Assmann, G. et al. (2007) Multiple QTL influence the serum Lp(a) concentration: a genome-wide linkage screen in the PROCARDIS study. Eur. J. Hum. Genet., 15, 221-227.
23. Ober, C., Nord, A.S., Thompson, E.E., Pan, L., Tan, Z., Cusanovich, D., Sun, Y., Nicolae, R., Edelstein, C., Schneider, D.H. et al. (2009) Genome-wide association study of plasma lipoprotein (a) levels identifies multiple genes on chromosome 6q. J. Lipid. Res., 50, 798-806.
24. Frazer, K.A., Ballinger, D.G., Cox, D.R., Hinds, D.A., Stuve, L.L., Gibbs, R.A., Belmont, J.W., Boudreau, A., Hardenbol, P., Leal, S.M. et al. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature, 449, 851-861.
25. Marchini, J. and Howie, B. (2010) Genotype imputation for genome-wide association studies. Nat. Rev. Genet., 11, 499-511.
26. Kronenberg, F. and Utermann, G. (2013) Lipoprotein(a): resurrected by genetics. J. Intern. Med., 273, 6-30.
27. Erqou, S., Thompson, A., Di Angelantonio, E., Saleheen, D., Kaptoge, S., Marcovina, S. and Danesh, J. (2010) Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J. Am. Coll. Cardiol., 55, 2160-2167.
28. Lanktree, M.B., Anand, S.S., Yusuf, S. and Hegele, R.A. (2009) Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample. J. Lipid Res., 50, 1487-1496.
29. Still, C.D., Wood, G.C., Chu, X., Erdman, R., Manney, C.H., Benotti, P.N., Petrick, A.T., Strodel, W.E., Mirshahi, U.L., Mirshahi, T. et al. (2011) High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery. Obesity (Silver Spring), 19, 1676-1683.
30. Kumashiro, N., Erion, D.M., Zhang, D., Kahn, M., Beddow, S.A., Chu, X., Still, C.D., Gerhard, G.S., Han, X., Dziura, J. et al. (2011) Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc. Natl. Acad. Sci. USA, 108, 16381-16385.
31. Pollin, T.I., Damcott, C.M., Shen, H., Ott, S.H., Shelton, J., Horenstein, R.B., Post, W., McLenithan, J.C., Bielak, L.F., Peyser, P.A. et al. (2008) A null mutation in human APOC3 confers a favorable plasma lipids profile and apparent cardioprotection. Science, 322, 1702-1705.
32. TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Crosby, J., Peloso, G.M., Auer, P.L., Crosslin, D.R., Stitziel, N.O., Lange, L.A., Lu, Y., Tang, Z.Z., Zhang, H., Hindy, G. et al. (2014) Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N. Engl. J. Med., 371, 22-31.
33. Jørgensen, A.B., Frikke-Schidt, R., Nordestgaard, B.G. and Tybjærg-Hansen, A. (2014) Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N. Engl. J. Med., 371, 32-41.
34. Rainwater, D.L. (1996) Lp(a) concentrations are related to plasma lipid concentrations. Atherosclerosis, 127, 13-18.
35. Koch, W., Mueller, J.C., Schrempf, M., Wolferstetter, H., Kirchhofer, J., Schomig, A. and Kastrati, A. (2013) Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene. Ann. Hum. Genet., 77, 47-55.
36. Zabaneh, D., Kumari, M., Sandhu, M., Wareham, N., Wainwright, N., Papamarkou, T., Hopewell, J., Clarke, R., Li, K., Palmen, J. et al. (2011) Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts. Atherosclerosis, 217, 447-451.
37. Lanktree, M.B., Rajakumar, C., Brunt, J.H., Koschinsky, M.L., Connelly, P.W. and Hegele, R.A. (2009) Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCR. J. Lipid Res., 50, 768-772.
38. Marcovina, S.M., Hobbs, H.H. and Albers, J.J. (1996) Relation between number of apolipoprotein(a) kringle 4 repeats and mobility of isoforms in agarose gel: basis for a standardized isoform nomenclature. Clin. Chem., 42, 436-439.
39. Kraft, H.G., Lingenhel, A., Kochl, S., Hoppichler, F., Kronenberg, F., Abe, A., Muhlberger, V., Schonitzer, D. and Utermann, G. (1996) Apolipoprotein(a) kringle IV repeat number predicts risk for coronary heart disease. Arterioscler. Thromb. Vasc. Biol., 16, 713-719.
40. Crawford, D.C., Peng, Z., Cheng, J.F., Boffelli, D., Ahearn, M., Nguyen, D., Shaffer, T., Yi, Q., Livingston, R.J., Rieder, M.J. et al. (2008) LPA and PLG sequence variation and kringle IV-2 copy number in two populations. Hum. Hered., 66, 199-209.
41. Luke, M.M., Kane, J.P., Liu, D.M., Rowland, C.M., Shiffman, D., Cassano, J., Catanese, J.J., Pullinger, C.R., Leong, D.U., Arellano, A.R. et al. (2007) A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler. Thromb. Vasc. Biol., 27, 2030-2036.
42. Ng, P.C. and Henikoff, S. (2003) SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res., 31, 3812-3814.
43. Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., Kondrashov, A.S. and Sunyaev, S.R. (2010) A method and server for predicting damaging missense mutations. Nat. Methods, 7, 248-249.
44. Cross, H.E. (1976) Population studies and the Old Order Amish. Nature, 262, 17-20.
45. Mitchell, B.D., McArdle, P.F., Shen, H., Rampersaud, E., Pollin, T.I., Bielak, L.F., Jaquish, C., Douglas, J.A., Roy-Gagnon, M.H., Sack, P. et al. (2008) The genetic response to short-term interventions affecting cardiovascular function: rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study. Am. Heart J., 155, 823-828.
46. Sorkin, J., Post, W., Pollin, T.I., O'Connell, J.R., Mitchell, B.D. and Shuldiner, A.R. (2005) Exploring the genetics of longevity in the Old Order Amish. Mech. Ageing Dev., 126, 347-350.
47. Kulkarni, K.R., Garber, D.W., Marcovina, S.M. and Segrest, J.P. (1994) Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J. Lipid Res., 35, 159-168.
48. Kulkarni, K.R. (2006) Cholesterol profile measurement by vertical auto profile method. Clin. Lab. Med., 26, 787-802.
49. Heard-Costa, N.L., Zillikens, M.C., Monda, K.L., Johansson, A., Harris, T.B., Fu, M., Haritunians, T., Feitosa, M.F., Aspelund, T., Eiriksdottir, G. et al. (2009) NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet., 5, e1000539.
50. Fu, M., Sabra, M.M., Damcott, C., Pollin, T.I., Ma, L., Ott, S., Shelton, J.C., Shi, X., Reinhart, L., O'Connell, J. et al. (2007) Evidence that Rho guanine nucleotide exchange factor 11 (ARHGEF11) on 1q21 is a type 2 diabetes susceptibility gene in the Old Order Amish. Diabetes, 56, 1363-1368.
51. Angles-Cano, E., Loyau, S., Cardoso-Saldana, G., Couderc, R. and Gillery, P. (1999) A novel kringle-4 number-based recombinant apo[a] standard for human apo[a] phenotyping. J. Lipid Res., 40, 354-359.
52. Schneider, C.A., Rasband, W.S. and Eliceiri, K.W. (2012) NIH Image to ImageJ: 25 years of image analysis. Nat. Methods, 9, 671-675.
53. Agarwala, R., Biesecker, L.G., Hopkins, K.A., Francomano, C.A. and Schaffer, A.A. (1998) Software for constructing and verifying pedigrees within large genealogies and an application to the Old Order Amish of Lancaster County. Genome Res., 8, 211-221.
54. Agarwala, R., Biesecker, L.G., Tomlin, J.F. and Schaffer, A.A. (1999) Towards a complete North American Anabaptist genealogy: A systematic approach to merging partially overlapping genealogy resources. Am. J. Med. Genet., 86, 156-161.