Skip to main content
SpringerLink
Log in

ApoB-100 R3500Q mutation in the Lebanese population: Prevalence and historical review of the literature

  • Original Paper
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

An interesting mutation affecting the Apo-B gene, R3500Q, is known to display variable geographical distribution in the world and is mostly implicated in the pathogenesis of Familial Hypercholesterolemia (FH). The aim of this study is to determine the prevalence of this mutation in the Lebanese population and compare it to the available international literature. DNA from 160 unrelated healthy donors from our HLA-bank was used and the ApoB genotype was determined using the CardioVascular Disease (CVD) StripAssay (this assay is based on a Polymerase Chain Reaction-Reverse Hybridization technique). The R3500Q mutation was not observed in the general Lebanese population. Since the mutation frequency is elevated in Central Europe and tends to decrease as one moves east and south, it disappears completely in the Mediterranean regions such as Spain, Turkey and Israel; therefore, it is rather expected to be absent in Lebanon as well. Our report adds a valuable piece of information regarding this mutation in an Arab country and paves the way for future research involving patients diagnosed with FH in order to assess the role of the R3500Q mutation in the development of this clinical entity.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Innerarity T, Mahley R, Weisgraber K et al (1990) Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia. J Lipid Res 31:1337–1349

    PubMed  CAS  Google Scholar 

  2. Tybjærg-Hansen A, Gallagher J, Vincent J, Houlston R, Talmud P, Dunning A et al (1990) Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. Atherosclerosis 80:235–242

    Article  PubMed  Google Scholar 

  3. Goldstein JL, Hobbs HH, Brown MS (1995) In: The metabolic and molecular bases of inherited disease, 7th edn. McGraw-Hill, New York, pp 1981–2030

    Google Scholar 

  4. Soria LF, Ludwig EH, Clarke HRG, Vega GL, Grundy SM, McCarty BJ (1989) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci USA 86:587–591

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Boren J, Ekstrom U, Agren B, Nilsson-Ehle P, Innerarity TL (2001) The molecular mechanism for the genetic disorder familial defective apolipoprotein B100. J Biol Chem 276:9214–9218

    Article  PubMed  CAS  Google Scholar 

  7. Blackhart B, Ludwig E, Pierotti V, Ciaiati L, Onasch M, Wallis S et al (1986) Structure of the human apolipoprotein B gene. J Biol Chem 261:15364–15367

    PubMed  CAS  Google Scholar 

  8. Innerarity T, Weisgraber K, Arnold K, Mahley R, Krauss R, Vega GL et al (1987) Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding. Proc Natl Acad Sci USA 84:6919–6923

    Article  PubMed  CAS  Google Scholar 

  9. Horvath A, Ganev V (2001) The mutation APOB-100 R3500Q in Eastern Europe. Atherosclerosis 156:241–242

    Article  PubMed  CAS  Google Scholar 

  10. Schuster H, Rauh G, Kormann B, Hepp T, Humphries S, Keller C et al (1990) Familial defective apolipoprotein B-100. Comparison with familial hypercholesterolemia in 18 cases detected in Munich. Arteriosclerosis 10:577–581

    PubMed  CAS  Google Scholar 

  11. Le Tensorer J-M, Niffeler U (1993) Verlag Schweizerische Gesellschaft für Ur- und Frühgeschichte, pp 203–241 (Deutsch)

  12. Myant N, Forbes S, Day I, Dallagher J (1997) Estimation of the age of the ancestral arginine3500-->glutamine mutation in human apoB-100. Genomics 45:78–87

    Article  PubMed  CAS  Google Scholar 

  13. Miserez AR, Laager R, Chiodetti N, Keller U (1994) High prevalence of familial defective apolipoprotein B-100 in Switzerland. J Lipid Res 35:574–583

    PubMed  CAS  Google Scholar 

  14. Kotze MJ, Peeters AV, Langenhoven E, Wauters JG, Van Gaal LF (1994) Phenotypic expression and frequency of familial defective apolipoprotein B-100 in Belgian hypercholesterolemics. Atherosclerosis 111:217–225

    Article  PubMed  CAS  Google Scholar 

  15. Bersot TP, Russell SJ, Thatcher SR, Pomernacki NK, Mahley RW, Weisgraber KH et al (1993) A unique haplotype of the apolipoprotein B-100 allele associated with familial defective apolipoprotein B-100 in a Chinese man discovered during a study of the prevalence of this disorder. J Lipid Res 34:1149–1154

    PubMed  CAS  Google Scholar 

  16. Hämälainen T, Palotie A, Aalto-Setala K, Kontula K, Tilkanen M (1990) Absence of familial defective apolipoprotein B-100 in Finnish patients with elevated serum cholesterol. Atherosclerosis 82:177–183

    Article  PubMed  Google Scholar 

  17. Seripa D, Gravina C, Volpe R, Margaglione M, Papa S, Merla G et al (1999) Absence of apolipoprotein B3500 mutation in type 2a hyperlipoproteinemia patients and in the general population from southern Italy. J Inherit Metab Dis 22:670–671

    Article  PubMed  CAS  Google Scholar 

  18. Real JT, Chaves JF, Ascaso JF, Armengod ME, Carmena R (1999) Familial defect of apo B-100 in subjects with clinically diagnosed primary hypercholesterolemia: identification of the first family with this disorder in Spain. Med Clin (Barc) 113:15–17 (Spanish)

    CAS  Google Scholar 

  19. Mahley RW, Palaoglu KE, Atak Z et al (1995) Turkish Heart Study: lipids, lipoproteins, and apolipoproteins. J Lipid Res 36:839–859

    PubMed  CAS  Google Scholar 

  20. Horvath A, Savov A, Kirov S et al (2001) High frequency of the ApoB-100 R3500Q mutation in Bulgarian hypercholesterolaemic subjects. J Med Genet 38(8):536–540

    Article  PubMed  CAS  Google Scholar 

  21. Zakharova FM, Damgaard D, Mandelshtam MY, Golubkov VI, Nissen PH, Nilsen GG et al (2005) Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia. BMC Med Genet 8:6

    Article  Google Scholar 

  22. Shevtsov SP (1996) Absence of DNA polymorphisms on the region of the APOV gene coding the proposed low density lipoprotein-binding domain of the ApoB-100 protein. Genetika 32:295–297 (Russian)

    Google Scholar 

  23. Krapivner SR, Malyshev PP, Rozhkova TA, Poltaraus AB, Kukharchuk VV, Bochkov VN (2000) Application of DNA analysis for differential diagnosis of familial hypercholesterolemia and familial defect of apolipoprotein b-100. Ter Arkh 72:9–12 (Article in Russian)

    Google Scholar 

  24. Dedoussis GV, Genschel J, Bochow B, Pitsavos C, Skoumas J, Prassa M et al (2004) Molecular characterization of familial hypercholesterolemia in German and Greek patients. Hum Mutat 23(3):285–286

    Article  PubMed  Google Scholar 

  25. Kalina A, Czeizel E, Romics L, Pados G, Reiber I, Dosa A et al (1998) Incidence of familial defective apolipoprotein B-100 in cases of patients diagnosed with familial hypercholesterolemia. Orv Hetil 139:755–759 (Article in Hangarian)

    PubMed  CAS  Google Scholar 

  26. Thiart R, Varret M, Lintott CJ, Scott RS, Loubser O, du Plessis L et al (2000) Mutation analysis in a small cohort of New Zealand patients originating from the United Kingdom demonstrates genetic heterogeneity in familial hypercholesterolemia. Mol Cell Probes 14(5):299–304

    Article  PubMed  CAS  Google Scholar 

  27. Teng YN, Pan JP, Chou SC, Tai DY, Lee-Chen GJ (2000) Familial defective apolipoprotein B-100: detection and haplotype analysis of the Arg(3500)– >Gln mutation in hyperlipidemic Chinese. Atherosclerosis 152(2):385–390

    Article  PubMed  CAS  Google Scholar 

  28. Friedlander Y, Dann EJ, Leitersdorf E (1993) Absence of familial defective apolipoprotein B-100 in Israeli patients with dominantly inherited hypercholesterolemia and in offspring with parental history of myocardial infarction. Hum Genet 91:299–300

    Article  PubMed  CAS  Google Scholar 

  29. Sozen MM, Whittall R, Oner C, Tokatli A, Kalkanoglu HS, Dursun A, Coskun T, Oner R, Humphries SE (2005) The molecular basis of familial hypercholesterolaemia in Turkish patients. Atherosclerosis 180(1):63–71

    Article  PubMed  Google Scholar 

  30. El Messal M, Ait Chihab K, Chater R, Vallve JC, Bennis F, Hafidi A et al (2003) Familial hypercholesterolemia in Morocco: first report of mutations in the LDL receptor gene. J Hum Genet 48(4):199–203

    Article  PubMed  CAS  Google Scholar 

  31. Castillo S, Tejedor D, Mozas P, Reyes G, Civeira F, Alonso R et al (2002) The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical diagnosis of familial hypercholesterolemia. Atherosclerosis 165(1):127–135

    Article  PubMed  CAS  Google Scholar 

  32. Gorski B, Kubalska J, Naruszewicz M, Lubinski J (1998) LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias. Hum Genet 102:562–565

    Article  PubMed  CAS  Google Scholar 

  33. Ceska R, Vrablik M, Horinek A (2000) Familial defective apolipoprotein B-100: a lesson from homozygous and heterozygous patients. Physiol Res 49(Suppl 1):S12

    Google Scholar 

  34. Kalina A, Császár A, Czeizel A et al (1998) Incidence of familial defective apolipoprotein B-100 in cases of patients diagnosed with familial hypercholesterolemia. Atherosclerosis 154:247–251

    Article  Google Scholar 

  35. Rosser ZH, Zerjal T, Hurles ME, Adojaan M, Alavantic D, Amorim A et al (2000) Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language. Am J Hum Genet 67(6):1526–1543

    Article  PubMed  CAS  Google Scholar 

  36. Miserez AR, Muller PY (2000) Familial defective apolipoprotein B-100: a mutation emerged in the mesolithic ancestors of Celtic peoples? Atherosclerosis 148:433–436

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Riad El Solh , P.O. Box 11-0236, 1107 2020, Beirut, Lebanon

    Amira S. Sabbagh, Rose T. Daher, Rabab N. Abdel Khalek, Ghazi S. Zaatari & Rami A. R. Mahfouz

  2. Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Zaher K. Otrock

Authors
  1. Amira S. Sabbagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rose T. Daher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zaher K. Otrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rabab N. Abdel Khalek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ghazi S. Zaatari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rami A. R. Mahfouz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rami A. R. Mahfouz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabbagh, A.S., Daher, R.T., Otrock, Z.K. et al. ApoB-100 R3500Q mutation in the Lebanese population: Prevalence and historical review of the literature. Mol Biol Rep 34, 267–270 (2007). https://doi.org/10.1007/s11033-006-9041-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-006-9041-7

Keywords

Search

Navigation