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Genome-wide Linkage Study for Plasma HDL Cholesterol Level in an Isolated Population of Mongolia

  • Park, Han-Soo (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Kim, Jong-Il (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Cho, Sung-Il (Seoul National University School of Public Health) ;
  • Sung, Joo-Hon (Seoul National University School of Public Health) ;
  • Kim, Hyung-Lae (Ewha Women's University) ;
  • Ju, Young-Seok (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Bayasgalan, Gombojav (Yonsei University College of Medicine) ;
  • Lee, Mi-Kyeong (Psoma Therapeutics Inc.) ;
  • Seo, Jeong-Sun (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
  • Published : 2008.03.31

Abstract

High-density lipoprotein (HDL) whose primary role is to transport cholesterol from peripheral tissues to the liver, is associated with the incidence of coronary heart disease. We analyzed HDL cholesterol levels in a genetically isolated population of extended Mongolian families. A total of 1002 individuals (54.5% women) from 95 families were enrolled. After genotyping by use of 1000 microsatellite markers, we performed a genome-wide linkage search with variance component analysis. The estimated heritability of HDL cholesterol was 0.45, revealing that HDL cholesterol was under significant genetic influence. We found peak evidence of linkage (LOD score=1.88) for HDL cholesterol level on chromosome 6 (nearest marker D6S1660) and potential evidences for linkage on chromosomes 1, 12 and 19 with the LOD scores of 1.32, 1.44 and 1.14, respectively. These results should pave the way for the discovery of the relevant genes by fine mapping and association analysis.

Keywords

References

  1. Almasy, L., et al. (1999). Human pedigree-based quantitative-trait-locus mapping: localization of two genes influencing HDL-cholesterol metabolism. Am. J. Human Genetics 64, 1686-1693. https://doi.org/10.1086/302425
  2. Aouizerat, B.E., et al. (1999). A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11. Am. J. Human Genetics 65, 397-412. https://doi.org/10.1086/302490
  3. Arya, R., et al. (2002). Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans. Nature Genetics 30, 102-105. https://doi.org/10.1038/ng810
  4. Barcat, D., et al. (2006). Combined hyperlipidemia/hyperalphalipoproteinemia associated with premature spontaneous atherosclerosis in mice lacking hepatic lipase and low density lipoprotein receptor. Atherosclerosis 188, 347-355. https://doi.org/10.1016/j.atherosclerosis.2005.11.022
  5. Bowry, V.W., Stanley, K.K., and Stocker, R. (1992). high-density-lipoprotein is the major carrier of lipid hydroperoxides in human blood-plasma from fasting donors. Proceedings of the National Academy of Sciences of the United States of America 89, 10316-10320. https://doi.org/10.1073/pnas.89.21.10316
  6. Brousseau, M.E., et al. (2004). Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N. Engl. J. Med. 350, 1505-1515. https://doi.org/10.1056/NEJMoa031766
  7. Coon, H., et al. (2001). Genome-wide linkage analysis of Hypertension Genetic Epidemiology Network (HyperGEN) Blood Pressure study. Arteriosclerosis Thrombosis and Vascular Biology 21, 1969-1976. https://doi.org/10.1161/hq1201.100228
  8. Dastani, Z., et al. (2006). Genetics of high-density lipoproteins. Current Opinion in Cardiology 21, 329-335. https://doi.org/10.1097/01.hco.0000231403.94856.cd
  9. Forwood, J.K., Harley, V., and Jans, D.A. (2001). The C-terminal nuclear localization signal of the sex determining region Y (SRY) high mobility group domain mediates nuclear import through beta 1. Journal of Biological Chemistry 276, 46575-46582. https://doi.org/10.1074/jbc.M101668200
  10. Heath, S.C. (1997). Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. American Journal of Human Genetics 61, 748-760. https://doi.org/10.1086/515506
  11. Imperatore, G., et al. (2000). A locus influencing total serum cholesterol on chromosome 19p - Results from an autosomal genomic scan of serum lipid concentrations in Pima Indians. Arteriosclerosis Thrombosis and Vascular Biology 20, 2651-2656. https://doi.org/10.1161/01.ATV.20.12.2651
  12. Inazu, A., et al. (1994). Genetic cholesteryl ester transfer protein-deficiency caused by 2 prevalent mutations as a major determinant of increased levels of high-density- lipoprotein cholesterol. Journal of Clinical Investigation 94, 1872-1882. https://doi.org/10.1172/JCI117537
  13. Klos, K.L., et al. (2001). Genome-wide linkage analysis reveals evidence of multiple regions that influence variation in plasma lipid and apolipoprotein levels associated with risk of coronary heart disease. Arteriosclerosis Thrombosis and Vascular Biology 21, 971-978. https://doi.org/10.1161/01.ATV.21.6.971
  14. Kuivenhoven, J.A., et al. (1997). Heterogeneity at the CETP gene locus - Influence on plasma CETP concentrations and HDL cholesterol levels. Arteriosclerosis Thrombosis and Vascular Biology 17, 560-568. https://doi.org/10.1161/01.ATV.17.3.560
  15. Mahaney, M.C., et al. (2003). A quantitative trait locus on chromosome 16q influences variation in plasma HDL-C levels in Mexican Americans. Arteriosclerosis Thrombosis and Vascular Biology 23, 339-345. https://doi.org/10.1161/01.ATV.0000051406.14162.6A
  16. Mari, M., and Cederbaum, A.I. (2001). Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress. Hepatology 33, 652-661. https://doi.org/10.1053/jhep.2001.22521
  17. Mcpeek, M.S., and Sun, L. (2000). Statistical tests for detection of misspecified relationships by use of genomescreen data. American Journal of Human Genetics 66, 1076-1094. https://doi.org/10.1086/302800
  18. Pajukanta, P., et al. (2003). Combined analysis of genome scans of Dutch and Finnish families reveals a susceptibility locus for high-density lipoprotein cholesterol on chromosome 16q. American Journal of Human Genetics 72, 903-917. https://doi.org/10.1086/374177
  19. Peacock, J.M., et al. (2001). Genome scan for quantitative trait loci linked to high-density lipoprotein cholesterol - The NHLBI family heart study. Arteriosclerosis Thrombosis and Vascular Biology 21, 1823-1828. https://doi.org/10.1161/hq1101.097804
  20. Shoulders, C.C., Jones, E.L., and Naoumova, R.P. (2004). Genetics of familial combined hyperlipidemia and risk of coronary heart disease. Human Molecular Genetics 13, R149-R160. https://doi.org/10.1093/hmg/ddh069
  21. Wang, X.S., and Paigen, B. (2005). Genome-wide search for new genes controlling plasma lipid concentrations in mice and humans. Current Opinion in Lipidology 16, 127-137. https://doi.org/10.1097/01.mol.0000162317.09054.9d
  22. Yamashita, S., et al. (2000). Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia. Atherosclerosis 152, 271-285. https://doi.org/10.1016/S0021-9150(00)00574-8
  23. Yancey, P.G., et al. (2003). Importance of different pathways of cellular cholesterol efflux. Arteriosclerosis Thrombosis and Vascular Biology 23, 712-719. https://doi.org/10.1161/01.ATV.0000057572.97137.DD

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