Coronary artery disease: evidence of interaction between PTPN22 and p53 genetic polymorphisms.
OBJECTIVE
We recently reported an association between the PTPN22 genetic polymorphism and coronary artery disease (CAD) in nondiabetic subjects. Since recent studies suggest that p53 may be involved in coronary atherosclerosis, we have investigated a possible interaction between PTPN22 and p53 codon 72 genetic polymorphisms regarding their effects on susceptibility to CAD in nondiabetic subjects.


METHODS
The genotypes of p53 codon 72 and PTPN22 were determined by DNA analysis in 128 nondiabetic subjects with CAD, 122 healthy blood donors and 117 nondiabetic subjects with cardiovascular diseases without CAD.


RESULTS
In subjects with the *Arg/*Arg genotype of p53 codon 72, no association was observed between CAD and PTPN22. However, this association was very strong in subjects carrying the *Pro allele of p53 codon 72. Subjects carrying both the *T allele of PTPN22 and the *Pro allele of p53 were overrepresented in CAD nondiabetic cases relative to the other two groups (p = 0.001).


CONCLUSIONS
Since both p53 and PTPN22 are involved in autoimmune inflammation, an interaction between the two systems appears biologically plausible. In the analysis of multifactorial disorders, the simultaneous analysis of multiple genes functionally related to diseases will provide a more productive approach than studies of single genetic factors performed from a Mendelian perspective.
Department of Biopathology and Imaging Diagnostics, University of Rome Tor Vergata, Rome, Italy.
P
P
Saccucci
M
M
Banci
A
A
Amante
E
E
Bottini
F
F
Gloria-Bottini
D000328:Adult; D000483:Alleles; D003062:Codon / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
D003062:Codon; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22