p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1

다국어 초록 (Multilingual Abstract)

Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination ofinhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an importantrole is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and theinteraction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthysubjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment lengthpolymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphismand allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is presentin subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype issignificantly high in asthmatic children than in controls (OR=1.941, 95% C.I. 1.042-3.628). Our finding could have important clinical implications sincethe subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype.

참고문헌 (Reference)

1 Pim D, "p53 polymorphic variants at codon 72 exert different effects on cell cycle progression" 108 : 196-199, 2004

2 Zheng SJ, "Tumor suppressor p53 inhibits autoimmune inflammation and macrophage function" 54 : 1423-1428, 2005

3 Hackett TL, "The role of epithelial injury and repair in the origins of asthma" 7 : 63-68, 2007

4 Dumont P, "The codon 72 polymorphic variants of p53 have markedly different apoptotic potential" 33 : 357-365, 2003

5 Holgate ST, "The airway epithelium is central to the pathogenesis of asthma" 57 : 1-10, 2008

6 이신화, "The Search for Genetic Variants and Epigenetics Related to Asthma" 대한천식알레르기학회 3 (3): 236-244, 2011

7 Trautmann A, "T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma" 109 : 329-337, 2002

8 Comhair SA, "Superoxide dismutase inactivation in pathophysiology of asthmatic airway remodeling and reactivity" 166 : 663-674, 2005

9 Uller L, "Resolution of airway disease: removal of inflammatory cells through apoptosis, egression or both?" 27 : 461-466, 2006

10 Benayoun L, "Regulation of peroxisome proliferator-activated receptor gamma expression in human asthmatic airways: relationship with proliferation, apoptosis, and airway remodeling" 164 : 1487-1494, 2001

11 Bottini N, "Low-molecularweight protein tyrosine phosphatase and human disease: in search of biochemical mechanisms" 50 : 95-104, 2002

12 Bottini N, "Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase" 63 : 228-231, 2003

13 Lazaruk KD, "Exon structure at the human ACP1 locus supports alternative splicing model for f and s isozyme generation" 196 : 440-446, 1993

14 Vignola AM, "Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis" 103 : 563-573, 1999

15 Barbato A, "Epithelial damage and angiogenesis in the airways of children with asthma" 174 : 975-981, 2006

16 Zhou C, "Epithelial apoptosis and loss in airways of children with asthma" 48 : 358-365, 2011

17 Walsh GM, "Defective apoptotic cell clearance in asthma and COPD--a new drug target for statins?" 29 : 6-11, 2008

18 Krysko DV, "Clearance of apoptotic and necrotic cells and its immunological consequences" 11 : 1709-1726, 2006

19 Lane DP, "Cancer. p53, guardian of the genome" 358 : 15-16, 1992

20 Busse WW, "Asthma" 344 : 350-362, 2001

21 Tattersfield AE, "Asthma" 360 : 1313-1322, 2002

22 Brutsche MH, "Apoptosis signals in atopy and asthma measured with cDNA arrays" 123 : 181-187, 2001

23 Jailwala P, "Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivation" 4 : e6527-, 2009

24 Trautmann A, "Apoptosis and loss of adhesion of bronchial epithelial cells in asthma" 138 : 142-150, 2005

25 Bottini E, "Allergy and ACP1 genetic polymorphism" 28 : 87-92, 2007

26 Vignola AM, "Airway remodeling in asthma" 123 : 417S-422S, 2003

27 James A, "Airway remodeling in asthma" 11 : 1-6, 2005

28 Bottini N, "Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP)" 277 : 24220-24224, 2002

29 de la Calle-Martín O, "AccII polymorphism of the p53 gene" 18 : 4963-, 1990

30 Bottini N, "ACP1 is associated with allergy" 57 : 651-652, 2002

31 Liu YG, "ACP1 genotype and asthma in the Chinese Han population" 137 : 263-264, 2005