Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian familial hypercholesterolemia patients

Atherosclerosis

Volumn 222, Issue 1, 2012, Pages 158-166

  Slimani, Afef ^a   Jelassi, Awatef ^a   Jguirim, Imen ^a   Najah, Mohamed ^a   Rebhi, Lamia ^b   Omezzine, Asma ^b   Maatouk, Faouzi ^c   Hamda, Khaldoun Ben ^c   Kacem, Maha ^d   Rabès, Jean Pierre ^e   Abifadel, Marianne ^f   Boileau, Catherine ^e,g   Rouis, Mustapha ^h   Slimane, Mohamed Naceur ^a   Varret, Mathilde ^g  

^a UNIVERSITY OF MONASTIR   (Tunisia)

^b SAHLOUL UNIVERSITY HOSPITAL   (Tunisia)

^c FATTOUMA BOURGUIBA UNIVERSITY HOSPITAL   (Tunisia)

^d FARHAT HACHED HOSPITAL   (Tunisia)

^e LABORATOIRE DES SCIENCES DU CLIMAT ET DE L ENVIRONNEMENT   (France)

^f SAINT JOSEPH UNIVERSITY   (Lebanon)

^g INSERM   (France)

^h SORBONNE UNIVERSITÉ   (France)

Author keywords

Familial hypercholesterolemia; LDLR gene; PCSK9 gene; Phenotypic variability

Indexed keywords

APOLIPOPROTEIN B100; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR;

ARTICLE; CHOLESTEROL BLOOD LEVEL; DISEASE SEVERITY; ENVIRONMENTAL FACTOR; FAMILIAL HYPERCHOLESTEROLEMIA; FRAMESHIFT MUTATION; GENE EXPRESSION; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HUMAN; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MEDICAL HISTORY; PHENOTYPE; PRIORITY JOURNAL; XANTHOMA;

ADOLESCENT; ADULT; APOLIPOPROTEINS E; CHILD; CHILD, PRESCHOOL; CHOLESTEROL, LDL; FEMALE; FRAMESHIFT MUTATION; HETEROZYGOTE; HOMOZYGOTE; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; MALE; MIDDLE AGED; MUTATION, MISSENSE; PEDIGREE; PHENOTYPE; PROPROTEIN CONVERTASES; RECEPTORS, LDL; SERINE ENDOPEPTIDASES; TUNISIA;

EID: 84859868297     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2012.02.018     Document Type: Article

References (36)

1. Goldstein J.L., Hobbs H.H., Brown M.S. Familial hypercholesterolemia. The metabolic and molecular bases of inherited disease 2001, 2863-2913. McGraw-Hill, New York. C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (Eds.).
2. Kane J.P., Havel R.J. Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins. The metabolic and molecular bases of inherited disease 2001, 2717-2752. McGraw-Hill, New York. C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (Eds.).
3. Abifadel M., Varret M., Rabès J.-P., et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003, 34:154-156.
4. Jelassi A., Slimani A., Jguirim I., et al. Moderate phenotypic expression of familial hypercholesterolemia in Tunisia. Clin Chim Acta 2010, 411:735-738.
5. Guardamagna O., Restagno G., Rolfo E., et al. The type of LDLR gene mutation predicts cardiovascular risk in children with familial hypercholesterolemia. J Pediatr 2009, 155:199-204.
6. Bertolini S., Pisciotta L., Di Scala L., et al. Genetic polymorphisms affecting the phenotypic expression of familial hypercholesterolemia. Atherosclerosis 2004, 174:57-65.
7. Jansen A.C., van Wissen S., Defesche J.C., Kastelein J.J. Phenotypic variability in familial hypercholesterolemia: an update. Curr Opin Lipidol 2002, 13:165-171.
8. Abifadel M., Rabès J.P., Devillers M., et al. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat 2009, 30(4):520-529.
9. Yue P., Averna M., Lin X., Schonfeld G. The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population. Hum Mutat 2006, 27:460-466.
10. Chen S.N., Ballantyne C.M., Gotto A.M., et al. A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis. J Am Coll Cardiol 2005, 45:1611-1619.
11. Aung L.H.H., Yin R.-X., Miao L., et al. The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Lipids Health Dis 2011, 10:2-15.
12. Miyake Y., Kimura R., Kokubo Y., et al. Genetic variants in PCSK9 in the Japanese population: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population. Atherosclerosis 2008, 196:29-36.
13. Eichner J.E., Dunn S.T., Perveen G., et al. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol 2002, 155:487-495.
14. Weisgraber K.H., Innerarity T.L., Mahley R.W. Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem 1982, 257:2518-2521.
15. Hatters D.M., Peters-Libeu C.A., Weisgraber K.H. Apolipoprotein E structure: insights into function. Trends Biochem Sci 2006, 31:445-454.
16. Jelassi A., Jguirim I., Najah M., et al. Limited mutational heterogeneity in the LDLR gene in familial hypercholesterolemia in Tunisia. Atherosclerosis 2009, 203:449-453.
17. Stephens M., Sloan J.S., Robertson P.D., Scheet P., Nickerson D.A. Automating sequence-based detection and genotyping of SNPs from diploid samples. Nat Genet 2006, 38:375-381.
18. Hixson J.E., Vernier D.T. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990, 31:545-548.
19. Slimane M.N., Lestavel S., Clavey V., et al. CYS127S (FH-Kairouan) and D245N (FH-Tozeur) mutations in the LDL receptor gene in Tunisian families with familial hypercholesterolaemia. J Med Genet 2002, 39:e74.
20. Hobbs H.H., Leitersdorf E., Leffert C.C., et al. Evidence for a dominant gene that suppresses hypercholesterolemia in a family with defective low density lipoprotein receptors. J Clin Invest 1989, 84:656-664.
21. Ekström U., Abrahamson M., Florén C.-H., et al. An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation C240F. Clin Genet 1999, 55:332-339.
22. Tosi I., Toledo-Leiva P., Neuwirth C., Naoumova R.P., Soutar A.K. Genetic defects causing familial hypercholesterolaemia: identification of deletions and duplications in the LDL-receptor gene and summary of all mutations found in patients attending the Hammersmith Hospital Lipid Clinic. Atherosclerosis 2007, 194:102-111.
23. Knoblauch H., Muller-Myhsok B., Busjahn A., et al. A cholesterol lowering gene maps to chromosome 13.q. Am J Hum Genet 2000, 66:157-166.
24. Abifadel M., Rabès J.P., Jambart S., et al. The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene. Hum Mutat 2009, 30:E682-E691.
25. Pisciotta L., Sallo R., Rabacchi C., et al. Leucine 10 allelic variant in signal peptide of PCSK9 increases the LDL cholesterol-lowering effect of statins in patients with familial hypercholesterolemia. Nutr Metab Cardiovasc Dis 2011, September 13, [Epub ahead of print].
26. Evans D., Beil F.U. The E670G SNP in the PCSK9 gene is associated with polygenic hypercholesterolemia in men but not in women. BMC Med Genet 2006, 7:66.
27. Norata G.D., Garlaschelli K., Grigore L., et al. Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles. Atherosclerosis 2010, 208:177-182.
28. Kotowski I.K., Pertsemlidis A., Luke A., et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet 2006, 78:410-422.
29. Scartezini M., Hubbart C., Whittall R.A., et al. The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men. Clin Sci (Lond) 2007, 113:435-441.
30. Strøm T.B., Holla Ø.L., Cameron J., Berge K.E., Leren T.P. Loss-of-function mutation R46L in the PCSK9 gene has little impact on the levels of total serum cholesterol in familial hypercholesterolemia heterozygotes. Clin Chim Acta 2010, 411(3-4):229-233.
31. Berge K.E., Ose L., Leren T.P. Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy. Arterioscler Thromb Vasc Biol 2006, 26:1094-1100.
32. Davignon J., Dubuc G. Statins and ezetimibe modulate plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels. Trans Am Clin Climatol Assoc 2009, 120:163-173.
33. Thompson J.F., Hyde C.L., Wood L.S. Comprehensive whole genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ Cardiovasc Genet 2009, 2:173-181.
34. Pisciotta L., Oliva C.P., Cefalu A.B., et al. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis 2006, 186:433-440.
35. Abifadel M., Bernier L., Dubuc G., et al. A PCSK9 variant and familial combined hyperlipidaemia. J Med Genet 2008, 45:780-786.
36. Huijgen R., Sjouke B., Vis K., et al. Genetic variation in APOB PCSK9, and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl Levels. Hum Mutat 2012, 33:448-455.