Search for genetic variants in the p66Shc longevity gene by PCR-single strand conformational polymorphism in patients with early-onset cardiovascular disease

详细信息    查看全文

• 作者：Federica Sentinelli (1) (2)
  Stefano Romeo (2)
  Fabrizio Barbetti (3)
  Andrea Berni (4)
  Emanuela Filippi (2)
  Marzia Fanelli (2)
  Mara Fallarino (2)
  Marco G Baroni (1)
  
• 刊名：BMC Genetics
• 出版年：2006
• 出版时间：December 2006
• 年：2006
• 卷：7
• 期：1
• 全文大小：1789KB
• 参考文献：1. Abe J, Berk BC: Reactive oxygen species as mediators of signal transduction in cardiovascular disease. / Trends Cardiovasc Med 1998, 8: 59-4. CrossRef
  2. Trinei M, Giorgio M, Cicalese A, Barozzi S, Ventura A, Migliaccio E, Milia E, Martin–Padura I, Raker VA, Maccarana M, Petronilli V, Minucci S, Bernardi P, Lanfrancone L, Pelicci PG: A p53–p66shc signaling pathway controls intracellular redox status, levels of oxidation–damaged DNA and oxidative stress–induced apoptosis. / Oncogene 2002, 21: 3872-878. CrossRef
  3. Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG: The p66shc adaptor protein controls oxidative stress response and life span in mammals. / Nature 1999, 402: 309-13. CrossRef
  4. Migliaccio E, Mele S, Salcini AE, Pelicci G, Lai KM, Superti–Fuga G, Pawson T, Di Fiore PP, Lanfrancone L, Pelicci PG: Opposite effects of the p52shc/p46shc and p66shc splicing isoforms on the EGF receptor MAP kinase–fos signaling pathway. / EMBO J 1997, 16: 706-16. CrossRef
  5. Zaccagnini G, Martelli F, Fasanaro P, Magenta A, Gaetano C, Di Carlo A, Biglioli P, Giorgio M, Martin–Padura I, Pelicci PG, Capogrossi MC: p66ShcA modulates tissue response to hindlimb ischemia. / Circulation 2004, 109: 2917-923. CrossRef
  6. Napoli C, Martin–Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, Condorelli M, Sica G, De Rosa G, Pelicci PG: Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high–fat diet. / Proc Natl Acad Sci 2003, 100: 2112-116. CrossRef
  7. Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Grignani F, Pawson T, Pelicci PG: A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. / Cell 1992, 70: 93-04. CrossRef
  8. Ventura A, Luzi L, Pacini S, Baldari CT, Pelicci PG: The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter. / J Biol Chem 2002, 277: 22370-2376. CrossRef
  9. Graiani G, Lagrasta C, Migliaccio E, Spillmann F, Meloni M, Madeddu P, Quaini F, Padura IM, Lanfrancone L, Pelicci P, Emanueli C: Genetic deletion of the p66Shc adaptor protein protects from angiotensin II–induced myocardial damage. / Hypertension 2005, 46: 433-40. CrossRef
  10. Francia P, delli Gatti C, Bachschmid M, Martin–Padura I, Savoia C, Migliaccio E, Pelicci PG, Schiavoni M, Luscher TF, Volpe M, Cosentino F: Deletion of p66shc gene protects against age–related endothelial dysfunction. / Circulation 2004, 110: 2889-5. CrossRef
  11. Rissanen AM: Familial occurrence of coronary artery disease: effect of age at diagnosis. / Am J Cardiol 1979, 44: 60-6. CrossRef
  12. Marenberg ME, Risch N, Berkman LF, Floderus B, De Faire U: Genetic susceptibility to death from coronary heart disease in a study of twins. / N Engl J Med 1994, 330: 1041-046. CrossRef
  13. Mooijaart SP, van Heemst D, Schreuder J, van Gerwen S, Beekman M, Brandt BW, Eline lagboom P, Westendorp RG, 'Long Life' Study Group: Variation in the SHC1 gene and longevity in humans. / Exp Gerontol 2004, 39: 263-68. CrossRef
  14. Almind K, Ahlgren MG, Hansen T, Urhammer SA, Clausen JO, Pedersen O: Discovery of a Met300Val variant in Shc and studies of its relationship to birth weight and length, impaired insulin secretion, insulin resistance, and type 2 diabetes mellitus. / J Clin Endocrinol Metab 1999, 84: 2241-244. CrossRef
  15. Rea IM, McKeown PP, McMaster D, Young IS, Patterson C, Savage MJ, Belton C, Marchegiani F, Olivieri F, Bonafe M, Franceschi C: Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis. / Exp Gerontol 2004, 39: 629-35. CrossRef
  16. Lio D, Candore G, Crivello A, Scola L, Colonna–Romano G, Cavallone L, Hoffmann E, Caruso M, Licastro F, Caldarera CM, Branzi A, Franceschi C, Caruso C: Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease. / J Med Genet 2004, 41: 790-94. CrossRef
  17. Terry DF, McCormick M, Andersen S, Pennington J, Schoenhofen E, Palaima E, Bausero M, Ogawa K, Perls TT, Asea A: Cardiovascular disease delay in centenarian offspring: role of heat shock proteins. / Ann N Y Acad Sci 2004, 1019: 502-05. CrossRef
  18. Rose GA, Blackburn H: / Cardiovascular Survey Methods. No 56 / 1 Edition Geneva (Switzerland): World Health Organization 1968.
  19. Sentinelli F, Lovari S, Vitale M, Giorgi G, Di Mario U, Baroni MG: A simple method for non–radioactive PCR–SSCP using MDE gel solution and a midi gel format: application for the detection of variants in the GLUT1 and CTLA- genes. / J Biotechnol 2000, 78: 201-04. CrossRef
  
• 作者单位：Federica Sentinelli (1) (2)
  Stefano Romeo (2)
  Fabrizio Barbetti (3)
  Andrea Berni (4)
  Emanuela Filippi (2)
  Marzia Fanelli (2)
  Mara Fallarino (2)
  Marco G Baroni (1)
  
  1. Department of Medical Sciences, Endocrinology, University of Cagliari, Cagliari, Italy
  2. Department of Clinical Sciences, Division of Endocrinology, University of Rome "La Sapienza", Rome, Italy
  3. IBCIT, Biomedical Scientific Park of Rome S Raffaele, Rome, Italy
  4. Department of Cardiology, II Faculty of Medicine, University of Rome "La Sapienza", Rome, Italy
  

文摘

Background Among the possible candidate genes for atherosclerosis experimental data point towards the longevity gene p66Shc. The p66Shc gene determines an increase of intracellular reactive oxygen species (ROS), affecting the rate of oxidative damage to nucleic acids. Knock-out p66Shc-/- mice show reduction of systemic oxidative stress, as well as of plasma LDL oxidation, and reduced atherogenic lesions. Thus, p66Shc may play a pivotal role in controlling oxidative stress and vascular dysfunction in vivo. Methods We searched for sequence variations in the p66Shc specific region of the Shc gene and its upstream promoter by PCR-SSCP in a selected group of early onset coronary artery disease (CAD) subjects (n. 78, mean age 48.5 ± 6 years) and in 93 long-living control subjects (mean age 89 ± 6 years). Results The analysis revealed two variant bands. Sequencing of these variants showed two SNPs: -354T>C in the regulatory region of p66Shc locus and 92C>T in the p66 specific region (CH2). Both these variants have never been described before. The first substitution partially modifies the binding consensus sequence of the Sp1 transcription factor, and was detected only in two heterozygous carriers (1 CAD subjects and 1 control subject). The 92C>T substitution in the CH2 region consists in an amino acid substitution at codon 31 (proline to leucine, P31L), and was detected in heterozygous status only in one CAD subject. No subjects homozygous for the two newly described SNPs were found. Conclusion Only two sequence variations in the p66Shc gene were observed in a total of 171 subjects, and only in heterozygotes. Our observations, in accordance to other studies, suggest that important variations in the p66Shc gene may be extremely rare and probably this gene is not involved in the genetic susceptibility to CAD.