Coronary Artery Disease: Evidence of Interaction between PTPN22 and p53 Genetic Polymorphisms

Abstract

Objectives: 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.

The association between peroxisome proliferator-activated receptor Δ rs3777744, rs3798343, and rs6922548 and coronary artery disease

“…P53 (also called TP53, tumor protein P53) is a widely studied protein-coding gene that is significantly related to neoplasms. In addition, P53, along with its functional polymorphism, has been linked to CAD in recent years [27–29].…”

TP53 single nucleotide polymorphism (rs1042522) in Iranian patients with coronary artery disease

“…probability of developing CAD (42,43). In this regard, genetic polymorphisms of the TP53 gene have been studied in CAD; however the results have so far been inconclusive (31,35,44). As a key tumor suppressor gene, the main function of TP53 is to protect the genome from damage.…”

“…Furthermore, TP53 also serves a role in autoimmune inflammation, and this may explain the link between the gene and developing CAD (32) Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) is among the known genes involved in autoimmune diseases including type 1 diabetes, celiac disease, rheumatoid arthritis and systemic lupus erythematosus (68,69). In this regard, accompaniment of a common SNP of PTPN22 (tryptophan 620 allele) and the TP53 Pro allele has been reported to be associated with atherosclerosis by Saccucci et al (44).…”

Association between Phosphatase Related Gene Variants and Coronary Artery Disease: Case-Control Study and Meta-Analysis

“…In addition to the three genes studied in this work, there are other phosphatase related genes implicated in CAD, for instance, the polymorphisms of phosphatase and tensin homologue ( PTEN ) gene are significantly associated with atherosclerotic cerebral infarction (ACI) in the Chinese population [42]. Genetic polymorphisms of the protein tyrosine phosphatase non-receptor 22 (PTPN22) are reported to be involved in atherosclerosis and played a role in the immune response involved in the pathogenesis of CAD [43,44]. The polymorphism of protein tyrosine phosphatase 1B (PTP1B) is associated with a decreased risk of CAD in the Han Chinese population [45], and the phosphodiesterase-1 (PC-1) variant was reported to be associated with metabolic syndrome in patients with CAD [46].…”