Role of PTPN2/22 polymorphisms in pathophysiology of Crohn’s disease

Figure 1 Shared genetic predispositions and environmental triggers between common inflammatory autoimmune disorders. For inflammatory autoimmune disorders, many share the same treatments and some of the same genetic single nucleotide polymorphisms in specific immunity genes. Thus, it is possible that these disorders share the same environmental triggers as well, such as Mycobacterium avium subspecies paratuberculosis (MAP) bacterial infection. CD: Crohn’s disease; PTPN2: Protein tyrosine phosphatase non-receptor type 2; PTPN22: Protein tyrosine phosphatase non-receptor type 22.

Figure 2 Allele frequency in nine single nucleotide polymorphisms in crohn’s disease and healthy control subjects. A: Represents allele frequency of PTPN2 SNPs: rs1893217, rs2542151, rs7234029, rs478582; B: Represents allele frequency of PTPN22 SNPs: rs2476601, rs2488457, rs33996649, rs34209542, rs2476599; C: Represents haplotype combinations PTPN2:rs478582 and PTPN22:rs2476601. ^aP < 0.05, healthy vs CD. T-G: Major/major; C-G: SNP/major; T-A: Major/SNP; C-A: SNP/SNP; SNPs: Single nucleotide polymorphisms; CD: Crohn’s disease; PTPN2: Protein tyrosine phosphatase non-receptor type 2; PTPN22: Protein tyrosine phosphatase non-receptor type 22.

Figure 3 Relative mRNA expression (2(^-∆CT) × 1000) of PTPN2, PTPN22 and IFN-γ. Relative mRNA expression of PTPN2 (A) and PTPN22 (B) in CD and healthy control subjects. Relative mRNA expression of IFN-γ was correlated with CD and healthy control subjects with either PTPN2:rs478582 (C) or PTPN22:2476601 (D). IFN-γ: Interferon-γ; CD: Crohn’s disease; PTPN2: Protein tyrosine phosphatase non-receptor type 2; PTPN22: Protein tyrosine phosphatase non-receptor type 22. ^aP < 0.05.

Figure 4 The effect of both Mycobacterium avium subspecies paratuberculosis and PTPN2:rs478582 on IFN-γ gene expression in Crohn’s disease and healthy control subjects. IFN-γ: Interferon-γ; CD: Crohn’s disease; MAP: Mycobacterium avium subspecies paratuberculosis; SNPs: Single nucleotide polymorphisms.

Figure 5 Complex interaction of Crohn’s disease pathophysiology. The effect of single nucleotide polymorphisms (SNPs) in Protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) and Mycobacterium avium subspecies paratuberculosis (MAP) in a dysregulated immune response in crohn’s disease (CD).