GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE and secondary associations with metabolic risk factors

Human Molecular Genetics

Volumn 20, Issue 22, 2011, Pages 4504-4514

  Benyamin, Beben ^a   Middelberg, Rita P ^a   Lind, Penelope A ^a   Valle, Anne M ^b   Gordon, Scott ^a   Nyholt, Dale R ^a   Medland, Sarah E ^a   Henders, Anjali K ^a   Heath, Andrew C ^c   Madden, Pamela A F ^c   Visscher, Peter M ^a   O'Connor, Daniel T ^b   Montgomery, Grant W ^a   Martin, Nicholas G ^a   Whitfield, John B ^a  

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOPEPTIDASE B; CHOLINESTERASE; GLUCOKINASE REGULATORY PROTEIN; GLUCURONOSYLTRANSFERASE 1A1; OXYGENASE; PROLINE RICH PROTEIN; PROTEIN ABI2; PROTEIN FTO; PROTEIN LAMELLIPODIN; REGULATOR PROTEIN; TRIACYLGLYCEROL; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; ARTICLE; BODY MASS; CARDIOVASCULAR RISK; CHROMOSOME 8; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; FEMALE; GENE LOCUS; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; GENOTYPE PHENOTYPE CORRELATION; HERITABILITY; HUMAN; MAJOR CLINICAL STUDY; MALE; METABOLIC SYNDROME X; PRIORITY JOURNAL; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADOLESCENT; ADULT; AMINOPEPTIDASES; BUTYRYLCHOLINESTERASE; CARRIER PROTEINS; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; GLUCURONOSYLTRANSFERASE; HUMANS; MALE; MEMBRANE PROTEINS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS; RISK FACTORS; YOUNG ADULT;

EID: 80054906871     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddr375     Document Type: Article

References (57)

1. Evans, F.T., Gray, P.W., Lehmann, H. and Silk, E. (1952) Sensitivity to succinylcholine in relation to serum cholinesterase. Lancet, 1, 1229-1230.
2. Jensen, F.S., Skovgaard, L.T. and Viby-Mogensen, J. (1995) Identification of human plasma cholinesterase variants in 6688 individuals using biochemical analysis. Acta Anaesthesiol. Scand., 39, 157-162.
3. Kutty, K.M., Huang, S.N. and Kean, K.T. (1981) Pseudocholinesterase in obesity: hypercaloric diet induced changes in experimental obese mice. Experientia, 37, 1141-1142.
4. Annapurna, V., Senciall, I., Davis, A.J. and Kutty, K.M. (1991) Relationship between serum pseudocholinesterase and triglycerides in experimentally induced diabetes mellitus in rats. Diabetologia, 34, 320-324.
5. Abbott, C.A., Mackness, M.I., Kumar, S., Olukoga, A.O., Gordon, C., Arrol, S., Bhatnagar, D., Boulton, A.J. and Durrington, P.N. (1993) Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus. Clin. Sci. (Lond.), 85, 77-81.
6. Kutty, K.M. and Payne, R.H. (1994) Serum pseudocholinesterase and very-low-density lipoprotein metabolism. J. Clin. Lab. Anal., 8, 247-250.
7. Rustemeijer, C., Schouten, J.A., Voerman, H.J., Beynen, A.C., Donker, A.J. and Heine, R.J. (2001) Is pseudocholinesterase activity related to markers of triacylglycerol synthesis in Type II diabetes mellitus? Clin. Sci. (Lond.), 101, 29-35.
8. Alcantara, V.M., Oliveira, L.C., Rea, R.R., Suplicy, H.L. and Chautard-Freire-Maia, E.A. (2005) Butyrylcholinesterase activity and metabolic syndrome in obese patients. Clin. Chem. Lab. Med., 43, 285-288.
9. Randell, E.W., Mathews, M.S., Zhang, H., Seraj, J.S. and Sun, G. (2005) Relationship between serum butyrylcholinesterase and the metabolic syndrome. Clin. Biochem., 38, 799-805.
10. Valle, A., O'Connor, D.T., Taylor, P., Zhu, G., Montgomery, G.W., Slagboom, P.E., Martin, N.G. and Whitfield, J.B. (2006) Butyrylcholinesterase: association with the metabolic syndrome and identification of 2 gene loci affecting activity. Clin. Chem., 52, 1014-1020.
11. Calderon-Margalit, R., Adler, B., Abramson, J.H., Gofin, J. and Kark, J.D. (2006) Butyrylcholinesterase activity, cardiovascular risk factors, and mortality in middle-aged and elderly men and women in Jerusalem. Clin. Chem., 52, 845-852.
12. Iwasaki, T., Yoneda, M., Nakajima, A. and Terauchi, Y. (2007) Serum butyrylcholinesterase is strongly associated with adiposity, the serum lipid profile and insulin resistance. Intern. Med., 46, 1633-1639.
13. Li, B., Duysen, E.G. and Lockridge, O. (2008) The butyrylcholinesterase knockout mouse is obese on a high-fat diet. Chem. Biol. Interact., 175, 88-91.
14. Podoly, E., Shalev, D.E., Shenhar-Tsarfaty, S., Bennett, E.R., Ben Assayag, E., Wilgus, H., Livnah, O. and Soreq, H. (2009) The butyrylcholinesterase K variant confers structurally derived risks for Alzheimer pathology. J. Biol. Chem., 284, 17170-17179.
15. Akizuki, S., Ohnishi, A., Kotani, K. and Sudo, K. (2004) Genetic and immunological analyses of patients with increased serum butyrylcholinesterase activity and its C5 variant form. Clin. Chem. Lab. Med., 42, 991-996.
16. Chautard-Freire-Maia, E.A., Primo-Parmo, S.L., Picheth, G., Lourenco, M.A. and Vieira, M.M. (1991) The C5 isozyme of serum cholinesterase and adult weight. Hum. Hered., 41, 330-339.
17. Hashim, Y., Shepherd, D., Wiltshire, S., Holman, R.R., Levy, J.C., Clark, A. and Cull, C.A. (2001) Butyrylcholinesterase K variant on chromosome 3 q is associated with Type II diabetes in white Caucasian subjects. Diabetologia, 44, 2227-2230.
18. Nassar, B.A., Darvesh, S., Bevin, L.D., Rockwood, K., Kirkland, S.A., O'Neill, B.J., Bata, I.R., Johnstone, D.E. and Title, L.M. (2002) Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease. Clin. Biochem., 35, 205-209.
19. Vaisi-Raygani, A., Rahimi, Z., Entezami, H., Kharrazi, H., Bahrhemand, F., Tavilani, H., Rezaei, M., Kiani, A., Nomanpour, B. and Pourmotabbed, T. (2008) Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran. Scand. J. Clin. Lab. Invest., 68, 123-129.
20. Freathy, R.M., Timpson, N.J., Lawlor, D.A., Pouta, A., Ben-Shlomo, Y., Ruokonen, A., Ebrahim, S., Shields, B., Zeggini, E., Weedon, M.N. et al. (2008) Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes, 57, 1419-1426.
21. Sturm, R.A., Duffy, D.L., Zhao, Z.Z., Leite, F.P., Stark, M.S., Hayward, N.K., Martin, N.G. and Montgomery, G.W. (2008) A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am. J. Hum. Genet., 82, 424-431.
22. Visel, A., Zhu, Y., May, D., Afzal, V., Gong, E., Attanasio, C., Blow, M.J., Cohen, J.C., Rubin, E.M. and Pennacchio, L.A. (2010) Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature, 464, 409-412.
23. Bartels, C.F., Jensen, F.S., Lockridge, O., van der Spek, A.F., Rubinstein, H.M., Lubrano, T. and La Du, B.N. (1992) DNA mutation associated with the human butyrylcholinesterase K-variant and its linkage to the atypical variant mutation and other polymorphic sites. Am. J. Hum. Genet., 50, 1086-1103.
24. O'Donnell, C.J., Cupples, L.A., D'Agostino, R.B., Fox, C.S., Hoffmann, U., Hwang, S.J., Ingellson, E., Liu, C., Murabito, J.M., Polak, J.F. et al. (2007) Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study. BMC Med. Genet., 8(Suppl. 1), S4.
25. Li, H., Schopfer, L.M., Masson, P. and Lockridge, O. (2008) Lamellipodin proline rich peptides associated with native plasma butyrylcholinesterase tetramers. Biochem. J., 411, 425-432.
26. Foulon, T., Cadel, S. and Cohen, P. (1999) Aminopeptidase B (EC 3.4.11.6). Int. J. Biochem. Cell Biol., 31, 747-750.
27. Lin, Y.C., Chang, P.F., Hu, F.C., Chang, M.H. and Ni, Y.H. (2009) Variants in the UGT1A1 gene and the risk of pediatric nonalcoholic fatty liver disease. Pediatrics, 124, e1221-e1227.
28. Middelberg, R.P., Martin, N.G. and Whitfield, J.B. (2007) A longitudinal genetic study of plasma lipids in adolescent twins. Twin Res. Hum. Genet., 10, 127-135.
29. Middelberg, R.P., Medland, S.E., Martin, N.G. and Whitfield, J.B. (2007) A longitudinal genetic study of uric acid and liver enzymes in adolescent twins. Twin Res. Hum. Genet, 10, 757-764.
30. Johansen, A., Nielsen, E.M., Andersen, G., Hamid, Y.H., Jensen, D.P., Glumer, C., Drivsholm, T., Borch-Johnsen, K., Jorgensen, T., Hansen, T. et al. (2004) Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion. Diabetologia, 47, 1437-1441.
31. Aulchenko, Y.S., Ripatti, S., Lindqvist, I., Boomsma, D., Heid, I.M., Pramstaller, P.P., Penninx, B.W., Janssens, A.C., Wilson, J.F., Spector, T. et al. (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat. Genet., 41, 47-55.
32. Kolz, M., Johnson, T., Sanna, S., Teumer, A., Vitart, V., Perola, M., Mangino, M., Albrecht, E., Wallace, C., Farrall, M. et al. (2009) Meta-analysis of 28 141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet., 5, e1000504.
33. Orho-Melander, M., Melander, O., Guiducci, C., Perez-Martinez, P., Corella, D., Roos, C., Tewhey, R., Rieder, M.J., Hall, J., Abecasis, G. et al. (2008) Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations. Diabetes, 57, 3112-3121.
34. Ridker, P.M., Pare, G., Parker, A., Zee, R.Y., Danik, J.S., Buring, J.E., Kwiatkowski, D., Cook, N.R., Miletich, J.P. and Chasman, D.I. (2008) Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. Am. J. Hum. Genet., 82, 1185-1192.
35. de la Iglesia, N., Mukhtar, M., Seoane, J., Guinovart, J.J. and Agius, L. (2000) The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. J. Biol. Chem., 275, 10597-10603.
36. Nogueiras, R., Wiedmer, P., Perez-Tilve, D., Veyrat-Durebex, C., Keogh, J.M., Sutton, G.M., Pfluger, P.T., Castaneda, T.R., Neschen, S., Hofmann, S.M. et al. (2007) The central melanocortin system directly controls peripheral lipid metabolism. J. Clin. Invest., 117, 3475-3488.
37. Staiger, H., Machicao, F., Schafer, S.A., Kirchhoff, K., Kantartzis, K., Guthoff, M., Silbernagel, G., Stefan, N., Haring, H.U. and Fritsche, A. (2008) Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function. PLoS ONE, 3, e3962.
38. Chambers, J.C., Elliott, P., Zabaneh, D., Zhang, W., Li, Y., Froguel, P., Balding, D., Scott, J. and Kooner, J.S. (2008) Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat. Genet., 40, 716-718.
39. Thorleifsson, G., Walters, G.B., Gudbjartsson, D.F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I. et al. (2009) Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet., 41, 18-24.
40. Willer, C.J., Speliotes, E.K., Loos, R.J., Li, S., Lindgren, C.M., Heid, I.M., Berndt, S.I., Elliott, A.L., Jackson, A.U., Lamina, C. et al. (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet., 41, 25-34.
41. Stancakova, A., Kuulasmaa, T., Paananen, J., Jackson, A.U., Bonnycastle, L.L., Collins, F.S., Boehnke, M., Kuusisto, J. and Laakso, M. (2009) Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5327 nondiabetic Finnish men. Diabetes, 58, 2129-2136.
42. Iizuka, K. and Horikawa, Y. (2008) ChREBP: a glucose-activated transcription factor involved in the development of metabolic syndrome. Endocr. J., 55, 617-624.
43. Prokopenko, I., Langenberg, C., Florez, J.C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R.J., Manning, A.K., Jackson, A.U., Aulchenko, Y. et al. (2009) Variants in MTNR1B influence fasting glucose levels. Nat Genet., 41, 77-81.
44. Bouatia-Naji, N., Bonnefond, A., Cavalcanti-Proenca, C., Sparso, T., Holmkvist, J., Marchand, M., Delplanque, J., Lobbens, S., Rocheleau, G., Durand, E. et al. (2009) A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet., 41, 89-94.
45. Olszewski, P.K., Fredriksson, R., Olszewska, A.M., Stephansson, O., Alsio, J., Radomska, K.J., Levine, A.S. and Schioth, H.B. (2009) Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC Neurosci., 10, 129.
46. Chistiakov, D.A. and Voronova, N.V. (2009) Zn(2+)-transporter-8: a dual role in diabetes. Biofactors, 35, 356-363.
47. Grundy, S.M., Brewer, H.B. Jr, Cleeman, J.I., Smith, S.C. Jr. and Lenfant, C. (2004) Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation, 109, 433-438.
48. Eddleston, M., Eyer, P., Worek, F., Sheriff, M.H. and Buckley, N.A. (2008) Predicting outcome using butyrylcholinesterase activity in organophosphorus pesticide self-poisoning. QJM, 101, 467-474.
49. Jintana, S., Sming, K., Krongtong, Y. and Thanyachai, S. (2009) Cholinesterase activity, pesticide exposure and health impact in a population exposed to organophosphates. Int. Arch. Occup. Environ. Health, 82, 833-842.
50. Kirk, K.M., Birley, A.J., Statham, D.J., Haddon, B., Lake, R.I., Andrews, J.G. and Martin, N.G. (2000) Anxiety and depression in twin and sib pairs extremely discordant and concordant for neuroticism: prodromus to a linkage study. Twin Res., 3, 299-309.
51. Treloar, S.A., Wicks, J., Nyholt, D.R., Montgomery, G.W., Bahlo, M., Smith, V., Dawson, G., Mackay, I.J., Weeks, D.E., Bennett, S.T. et al. (2005) Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26. Am. J. Hum. Genet., 77, 365-376.
52. Heath, A.C., Whitfield, J.B., Martin, N.G., Pergadia, M.L., Goate, A.M., Lind, P.A., McEvoy, B.P., Schrage, A.J., Grant, J.D., Chou, Y.L. et al. (2011) A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications. Biol. Psychiatry [Epub ahead of print].
53. Ellman, G.L., Courtney, K.D., Andres, V. Jr. and Feather-Stone, R.M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 7, 88-95.
54. Benyamin, B., Ferreira, M.A., Willemsen, G., Gordon, S., Middelberg, R.P., McEvoy, B.P., Hottenga, J.J., Henders, A.K., Campbell, M.J., Wallace, L. et al. (2009) Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat. Genet., 41, 1173-1175.
55. Medland, S.E., Nyholt, D.R., Painter, J.N., McEvoy, B.P., McRae, A.F., Zhu, G., Gordon, S.D., Ferreira, M.A., Wright, M.J., Henders, A.K. et al. (2009) Common variants in the trichohyalin gene are associated with straight hair in Europeans. Am. J. Hum. Genet., 85, 750-755.
56. Chen, W.M. and Abecasis, G.R. (2007) Family-based association tests for genomewide association scans. Am. J. Hum. Genet., 81, 913-926.
57. Willer, C.J., Li, Y. and Abecasis, G.R. (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics, 26, 2190-2191.