Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia

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art_SANTOS_Presence_and_type_of_low_density_lipoprotein_receptor_2014.PDF (228.59 KB)
Citações na Scopus
53
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER IRELAND LTD
Autores
MORGAN, Aline Cruz
Citação
ATHEROSCLEROSIS, v.233, n.1, p.206-210, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused mainly by LDLR mutations. This study assessed the influence of the presence and type of LDLR mutation on lipid profile and the response to lipid-lowering therapy in Brazilian patients with heterozygous FH. Methods: For 14 +/- 3 months, 156 patients with heterozygous FH receiving atorvastatin were followed. Coding sequences of the LDLR gene were bidirectionally sequenced, and the type of LDLR mutations were classified according to their probable functional class. Results: The frequencies of the types of LDLR mutations were: null-mutation (n = 40, 25.6%), defective-mutation (n = 59, 37.8%), and without an identified mutation (n = 57, 36.6%). Baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were higher in patients carrying a null mutation (9.9 +/- 1.9 mmol/L, 7.9 +/- 1.7 mmol/L), compared to those with a defective (8.9 +/- 2.2 mmol/L, 7.0 +/- 2.0 mmol/L), or no mutation (7.9 +/- 1.9 mmol/L, 5.8 +/- 1.9 mmol/L) (p < 0.001). After treatment, the proportion of patients attaining an LDL-C<3.4 mmol/L was significantly different among groups: null (22.5%), defective (27.1%), and without mutations (47.4%) (p = 0.02). The presence of LDLR mutations was independently associated with higher odds of not achieving the LDL-C cut-off (OR 9.07, 95% CI 1.41-58.16, p = 0.02). Conclusions: Our findings indicate that the presence and type of LDLR mutations influence lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous FH. Thus, more intensive care with pharmacological therapeutics should be performed in patients who have a molecular analysis indicating the presence of a LDLR mutation. (C) 2014 Published by Elsevier Ireland Ltd.
Palavras-chave
LDLR gene, Lipid-lowering therapy, Familial hypercholesterolemia, Type of mutation
URI
https://observatorio.fm.usp.br/handle/OPI/5340
Referências
  1. Alonso R, 2008, ATHEROSCLEROSIS, V200, P315, DOI 10.1016/j.atherosclerosis.2007.12.024
  2. Alvim RO, 2010, LIPIDS HEALTH DIS, V9, DOI 10.1186/1476-511X-9-128
  3. Bertolini S, 2000, ARTERIOSCL THROM VAS, V20, pE41
  4. Bertolini S, 1999, ARTERIOSCL THROM VAS, V19, P408
  5. Chaves FJ, 2001, J CLIN ENDOCR METAB, V86, P4926, DOI 10.1210/jc.86.10.4926
  6. Choumerianou DM, 2005, CLIN CHEM LAB MED, V43, P793, DOI 10.1515/CCLM.2005.134
  7. Baigent C, 2005, LANCET, V366, P1267, DOI 10.1016/S0140-6736(05)67394-1
  8. Couture P, 1998, ARTERIOSCL THROM VAS, V18, P1007
  9. Ghatak A, 2010, ATHEROSCLEROSIS, V210, P337, DOI 10.1016/j.atherosclerosis.2009.11.033
  10. Heath KE, 1999, ATHEROSCLEROSIS, V143, P41, DOI 10.1016/S0021-9150(98)00274-3
  11. HOBBS HH, 1990, ANNU REV GENET, V24, P133, DOI 10.1146/annurev.ge.24.120190.001025
  12. Hobbs Helen H., 1992, Human Mutation, V1, P445, DOI 10.1002/humu.1380010602
  13. Huijgen Roeland, 2008, Expert Rev Cardiovasc Ther, V6, P567, DOI 10.1586/14779072.6.4.567
  14. JEENAH M, 1993, ATHEROSCLEROSIS, V98, P51, DOI 10.1016/0021-9150(93)90222-G
  15. Santos PCJL, 2011, BMC MED GENET, V12, DOI 10.1186/1471-2350-12-136
  16. Leigh SEA, 2008, ANN HUM GENET, V72, P485, DOI 10.1111/j.1469-1809.2008.00436.x
  17. LEITERSDORF E, 1993, CIRCULATION, V87, P35
  18. Link E, 2008, NEW ENGL J MED, V359, P789
  19. Mata N, 2011, LIPIDS HEALTH DIS, V10, DOI 10.1186/1476-511X-10-94
  20. Miltiadous George, 2005, Pharmacogenet Genomics, V15, P219, DOI 10.1097/01213011-200504000-00005
  21. Mozas Pilar, 2004, Hum Mutat, V24, P187, DOI 10.1002/humu.9264
  22. Niemi M, 2011, PHARMACOL REV, V63, P157, DOI 10.1124/pr.110.002857
  23. Nordestgaard BG, 2013, EUR HEART J
  24. Pijlman AH, 2010, ATHEROSCLEROSIS, V209, P189, DOI 10.1016/j.atherosclerosis.2009.09.014
  25. Santos PCJD, 2011, AM J HYPERTENS, V24, P278, DOI 10.1038/ajh.2010.244
  26. Santos PCJL, 2012, EUR J CLIN PHARMACOL, V68, P273, DOI 10.1007/s00228-011-1125-1
  27. Santos RD, 2013, ARQ BRAS CARDIOL, V99, P1
  28. Schaefer Juergen R, 2012, Clin Res Cardiol Suppl, V7, P2
  29. Sijbrands EJG, 1998, ATHEROSCLEROSIS, V136, P247, DOI 10.1016/S0021-9150(97)00216-5
  30. Sun XM, 1998, ATHEROSCLEROSIS, V136, P175, DOI 10.1016/S0021-9150(97)00181-0
  31. Torres AL, 1996, ATHEROSCLEROSIS, V126, P163
  32. Vohl MC, 2002, ATHEROSCLEROSIS, V160, P361, DOI 10.1016/S0021-9150(01)00584-6
  33. WILLIAMS RR, 1993, AM J CARDIOL, V72, P171, DOI 10.1016/0002-9149(93)90155-6

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13