although the inflammatory theory of atherosclerosis is the most prominent , several observations point to common biological features between cancer and atherosclerosis [ 14 ] . this has suggested a possible relationship between atherosclerosis and p53 , a protein well known for its association with cancer [ 510 ] . at present , however , the data on such a relationship are controversial , suggesting interactions with other variables . the genetic analysis of multifactorial disorders represents a central problem in medical genetics , and the study of single gene factors based on a mendelian perspective is reductionist and unable to solve the problem . the simultaneous analysis of multiple genes functionally related to the disease , and of environmental factors involved in the susceptibility to a disease , is likely to provide a more productive approach . recently , we have found an association between cad and acid phosphatase locus 1 ( acp1 ) , an enzyme involved in glucose metabolism , cellular growth and cancer development ( 13 ) . acp1 is a polymorphic gene with 3 codominant alleles ( * a,*b,*c ) at an autosomal locus that controls the synthesis of the cytosolic low molecular weight protein tyrosine phosphatase ( clmwptp ) . there are 6 genotypes with enzymatic activity , increasing in the order * a/*a<*a/*b<*b/ * b=*a/*c<*b/*c<*c/*c ; the last genotype is very rare . the enzyme discloses 2 isoforms  f and s  that have different biochemical properties and different concentrations between genotypes ; carriers of * c allele have the highest concentration of s isoform . the acp1 enzyme dephosphorylates a negative regulatory phosphorylation site in the zap-70 tyrosine kinase in t cells , an event that leads to increased activation of this kinase and enhanced signaling from the t cell antigen receptor . codon 72 in exon 4 of the p53 gene shows a polymorphism characterized by a g to c substitution that determines the change of arginine to proline in the protein . the amino acidic change affects biochemical and functional properties of p53 : the arginine variant is a stronger apoptosis inducer , while the proline variant is a stronger transcriptional activator . recent studies point to an involvement of the protein in functions of the immune system . in the present study we searched for a possible interaction between acp1 and p53 we studied 381 subjects admitted for cardiovascular diseases to the valmontone hospital , rome , italy  232 patients with coronary artery disease and 149 with other cardiovascular problems . tables 1 and 2 show some clinical data for the 2 classes of patients . a small sample of 97 newborn infants was also studied . acp1 genotypes were determined as previously described   and p53 codon 72 genotype was determined according to the method of de la calle - martin et al . . statistical analyses were carried out by spss programs . written informed consent was obtained from patients or from their mothers to participate to this study that was approved by the hospital ethics committee . table 3 shows the distribution of p53 codon 72 genotypes in cad and non - cad patients in relation to acp1 genotypes , grouped according to total enzymatic activity . there is a significant association between acp1 and p53 in cad but not in non - cad . this interaction depends on the association between high acp1 activity * b/*c genotype with * pro carrier genotypes , which is statistically significant in cad but not in non - cad patients . the data suggest a positive effect of * pro allele of p53 codon 72 on susceptibility to cad , but only in the presence of the acp1 genotype with high enzymatic activity . table 4 shows the proportion of the joint genotype  * pro carrier of p53 codon 72/ * b*c genotype  in cad , in non - cad patients , and in newborn infants . the proportion of this joint genotype is higher in cad than in non - cad , while an intermediate value is observed in newborns . the value observed in newborns corresponds to that expected on the basis of acp1 and p53 codon 72 genotype frequency in the general population ( figure 1 ) . we have examined possible effects of the following variables : sex , age , diabetes , hypertension , history of previous infarction and smoking . in the cad sample no significant effect of these variables was observed on the proportion of * pro carriers with the * b*c genotype . the results of our study suggest that a relationship between p53 codon 72 polymorphism and cad may indeed exist and that it is influenced by acp1 . the joint genotype * pro carrier/*b/*c in newborns shows an intermediate value between cad and non - cad patients . this could be explained by considering that a certain proportion of newborns will have coronary artery disease in adult life . to study the role of genetic factors on susceptibility to cad , adult subjects with cardiovascular disease without cad recent studies suggest that p53 is involved in autoimmune inflammation   regulating stat1 and pro - inflammatory cytokines . on the other hand , acp1 , through regulation of zap-70 , overall , it seems that acp1 * b/*c subjects carrying the * pro allele are more vulnerable to cad than other joint genotypes . * pro allele of p53 codon 72 , with its strong properties of transcriptional activation , could aggravate local coronary inflammatory lesions stimulated by enhanced signalling from t cell antigen receptors due to high acp1 activity . a limitation of the present study is the relatively small size of study samples . moreover , although no significant effect of several risk factors for cad have been detected for the proportion of p53 * pro carriers with * b/*c genotype , in cad these effects should be carefully evaluated in a larger sample . if confirmed , our observation may have important implications for the evaluation of risk for cad and could suggest a target for prevention and/or treatment .
summarybackgroundcommon biological features between cancer and atherosclerosis suggest possible association of p53 with atherosclerotic diseases , but data on such a relationship are controversial , suggesting interactions with other variables . 
 acid phosphatase locus 1 ( acp1 ) is a polymorphic gene that controls the synthesis of an enzyme involved in important metabolic functions . 
 since acp1 is associated with coronary artery disease ( cad ) , we searched for possible interactions between this enzyme and p53 codon 72 polymorphism with regard to their effects on susceptibility to cad.material/methodsthe study included 381 patients admitted to the hospital for cardiovascular disease ( 232 patients with cad and 149 with other cardiovascular problems ) and 97 healthy newborns.resultsthe proportion of subjects carrying the * pro allele of p53 codon 72 and the high activity * b*c genotype of acp1 is higher in cad ( 10.3% ) than in non - cad patients ( 2.0% ) and in healthy newborns ( 6.2%).conclusionsthe data suggest an interaction between p53 codon 72 and acp1 wherein a positive effect of the p53 * pro allele on susceptibility to cad occurs , but only in the presence of the acp1 genotype characterized by high enzymatic activity .