Skip to main content
SpringerLink
Log in

Detection of Defective Apolipoprotein B-100 R3500Q Mutation Caused Familial Hypercholesterolemia in Vietnamese Patients

  • Conference paper
  • First Online:
6th International Conference on the Development of Biomedical Engineering in Vietnam (BME6) (BME 2017)

Part of the book series: IFMBE Proceedings ((IFMBE,volume 63))

Abstract

Familial defective apolipoprotein B-100 (FDB) is an autosomal codominant disorder associated with hypercholesterolemia, caused by mutations in and around codon 3500 of the Apolipoprotein (Apo) B gene, which encodes Apo B-100. The first mutation occurred in Arginine codons to be described, and the most characterized, is caused by a G→A transition at nucleotide 10,708 leading to the substitution of Arginine by Glutamine at codon 3500 (ApoB R3500Q). In this study, we have applied PCR-Sequencing to identify 27/40 R3500Q mutations in known FDB patients, counting for 68%, in which, most of the patients carried heterozygous mutation R3500Q, 25/27 cases. PCR-Sequencing method that we have applied for this study proved consistent and fast method to identify mutations correctly.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232(4746):34–47

    Article  Google Scholar 

  2. Choong ML, Koay ES, Khoo KL, Khaw MC, Sethi SK (1997) Denaturing gradient-gel electrophoresis screening of familial defective apolipoprotein B-100 in a mixed Asian cohort: two cases of arginine3500 →tryptophan mutation associated with a unique haplotype. Clin Chem 43(6 Pt 1):916–923

    Google Scholar 

  3. Dedoussis GV, Genschel J, Bochow B, Pitsavos C, Skoumas J, Prassa M, Lkhagvasuren S, Toutouzas P, Vogt A, Kassner U, Thomas HP, Schmidt H (2004) Molecular characterization of familial hypercholesterolemia in German and Greek patients. Hum Mutat 23(3):285–286

    Article  Google Scholar 

  4. Fisher E, Scharnagl H, Hoffmann MM, Kusterer K, Wittmann D, Wieland H, Gross W, März W (1999) Mutations in the apolipoprotein (apo) B-100 receptor-binding region: detection of apo B-100 (Arg3500→Trp) associated with two new haplotypes and evidence that apo B-100 (Glu3405→Gln) diminishes receptor-mediated uptake of LDL. Clin Chem 45(7):1026–1038

    Google Scholar 

  5. Friedl W, Ludwig EH, Balestra ME, Arnold KS, Paulweber B, Sandhofer F, McCarthy BJ, Innerarity TL (1991) Apolipoprotein B gene mutations in Austrian subjects with heart disease and their kindred. Arterioscler Thromb 11(2):371–378

    Article  Google Scholar 

  6. Futema M, Plagnol V, Whittall RA, Neil HA (2012) Use of targeted exome sequencing as a diagnostic tool for Familial Hypercholesterolaemia. J Med Genet 49(10):644–649

    Article  Google Scholar 

  7. Futema M, Whittall RA, Kiley A, Steel LK, Cooper JA, Badmus E, Leigh SE, Karpe F, Neil HA, Simon Broome Register Group, Humphries SE (2013) Analysis of the frequency and spectrum of mutations recognised to cause familial hypercholesterolaemia in routine clinical practice in a UK specialist hospital lipid clinic. Atherosclerosis 229(1):161–168

    Article  Google Scholar 

  8. García-García AB, Real JT, Puig O, Cebolla E, Marín-García P, Martínez Ferrandis JI, García-Sogo M, Civera M, Ascaso JF, Carmena R, Armengod ME, Chaves FJ (2001) Molecular genetics of familial hypercholesterolemia in Spain: ten novel LDLR mutations and population analysis. Hum Mutat 18(5):458–459

    Article  Google Scholar 

  9. Heath KE, Humphries SE, Middleton-Price H, Boxer M (2001) A molecular genetic service for diagnosing individuals with familial hypercholesterolaemia (FH) in the United Kingdom. Eur J Hum Genet 9(4):244–252

    Article  Google Scholar 

  10. Henderson BG, Wenham PR, Ashby JP, Blundell G (1997) Detecting familial defective apolipoprotein B-100: three molecular scanning methods compared. Clin Chem 43(9):1630–1634

    Google Scholar 

  11. Hevonoja T, Pentikäinen MO, Hyvönen MT, Kovanen PT, Ala-Korpela M (2000) Structure of low density lipoprotein (LDL) particles: basis for understanding molecular changes in modified LDL. Biochim Biophys Acta 1488(3):189–210

    Article  Google Scholar 

  12. Horvath A, Savov A, Kirov S, Karshelova E, Paskaleva I, Goudev A, Ganev V (2001) High frequency of the ApoB-100 R3500Q mutation in Bulgarian hypercholesterolaemic subjects. J Med Genet 38(8):536–540

    Article  Google Scholar 

  13. Innerarity TL, Mahley RW, Weisgraber KH, Bersot TP, Krauss RM, Vega GL (1990) Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolaemia. J Lipid Res 31(8):1337–1349

    Google Scholar 

  14. Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network, Boileau C, Varret M, Rabès JP (2010) Molecular spectrum of autosomal dominant hypercholesterolemia in France. Hum Mutat 31(11):E1811–E1824

    Article  Google Scholar 

  15. Myant NB (1993) Familial defective apolipoprotein B-100: including some comparisons with familial hypercholesterolaemia. Atherosclerosis 104(1–2):1–18

    Article  Google Scholar 

  16. Pullinger CR, Hennessy LK, Chatterton JE, Liu W, Love JA, Mendel CM, Frost PH, Malloy MJ, Schumaker VN, Kane JP (1995) Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity. J Clin Invest 95(3):1225–1234

    Article  Google Scholar 

  17. Rabès JP, Varret M, Devillers M, Aegerter P, Villéger L, Krempf M, Junien C, Boileau C (2000) R3531C mutation in the apolipoprotein B gene is not sufficient to cause hypercholesterolemia. Arterioscler Thromb Vasc Biol 20(10):E76–E82

    Article  Google Scholar 

  18. Real JT, Chaves FJ, Ejarque I, García-García AB, Valldecabres C, Ascaso JF, Armengod ME, Carmena R (2003) Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population. Eur J Hum Genet 11(12):959–965

    Article  Google Scholar 

  19. Tai DY, Pan JP, Lee-Chen GJ (1998) Identification and haplotype analysis of apolipoprotein B-100 Arg3500→Trp mutation in hyperlipidemic Chinese. Clin Chem 44(8 Pt 1):1659–1665

    Google Scholar 

  20. Tai ES, Koay ES, Chan E, Seng TJ, Loh LM, Sethi SK, Tan CE (2001) Compound heterozygous familial hypercholesterolemia and familial defective apolipoprotein B-100 produce exaggerated hypercholesterolemia. Clin Chem 47(3):438–443

    Google Scholar 

  21. Thiart R, Scholtz CL, Vergotine J, Hoogendijk CF, de Villiers JN, Nissen H, Brusgaard K, Gaffney D, Hoffs MS, Vermaak WJ, Kotze MJ (2000) Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia. J Med Genet 37(7):514–519

    Article  Google Scholar 

  22. Thomas ER, Atanur SS, Norsworthy PJ, Encheva V, Snijders AP, Game L, Vandrovcova J, Siddiq A, Seed M, Soutar AK, Aitman TJ (2013) Identification and biochemical analysis of a novel APOB mutation that causes autosomal dominant hypercholesterolemia. Mol Genet Genomic Med 1(3):155–161

    Article  Google Scholar 

  23. Tybjaerg-Hansen A, Humphries SE (1992) Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolaemia and premature coronary artery disease. Atherosclerosis 96(2–3):91–107

    Article  Google Scholar 

  24. Tybjaerg-Hansen A, Steffensen R, Meinertz H, Schnohr P, Nordestgaard BG (1998) Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease. N Engl J Med 338(22):1577–1584

    Article  Google Scholar 

  25. Wang J, Ban MR, Hegele RA (2005) Multiplex ligation-dependent probe amplification of LDLR enhances molecular diagnosis of familial hypercholesterolemia. J Lipid Res 46(2):366–372

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Ho Chi Minh City Open University Fund. The assistance of the Xuyen A Hospital and Thu Duc Hospital, Vietnam, are also gratefully acknowledged.

Author information

Authors and Affiliations

  1. Ho Chi Minh City Open University, Ho Chi Minh, Vietnam

    Phuong Kim Truong, Thuan Duc Lao & Thuy Huyen Ai Le

  2. University of Science, Ho Chi Minh City, Vietnam

    Cong Van Bui

Authors
  1. Phuong Kim Truong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cong Van Bui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thuan Duc Lao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thuy Huyen Ai Le
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thuy Huyen Ai Le .

Editor information

Editors and Affiliations

  1. Biomedical Engineering Department, Vietnam National University, Ho Chi Minh , Ho Chi Minh City, Vietnam

    Toi Vo Van

  2. Department of Biomedical Engineering, Vietnam National University, Ho Chi Minh Department of Biomedical Engineering, Ho Chi Minh City, Vietnam

    Thanh An Nguyen Le

  3. Biomedical Engineering Department, Vietnam National University, Ho Chi Minh Biomedical Engineering Department, Ho Chi Minh City, Vietnam

    Thang Nguyen Duc

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this paper

Cite this paper

Truong, P.K., Van Bui, C., Lao, T.D., Le, T.H.A. (2018). Detection of Defective Apolipoprotein B-100 R3500Q Mutation Caused Familial Hypercholesterolemia in Vietnamese Patients. In: Vo Van, T., Nguyen Le, T., Nguyen Duc, T. (eds) 6th International Conference on the Development of Biomedical Engineering in Vietnam (BME6) . BME 2017. IFMBE Proceedings, vol 63. Springer, Singapore. https://doi.org/10.1007/978-981-10-4361-1_46

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-4361-1_46

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-4360-4

  • Online ISBN: 978-981-10-4361-1

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation