AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples...AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms(SNPs) in PTPN2/22 using TaqMan^(?) genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis(MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin(PHA) mitogen or mycobacterial antigens by Brd U proliferation assays for T-cell activity. RESULTS Out of the nine SNPs examined, subjects with either heterozygous(TC)/minor(CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls(P-values < 0.05; OR = 3.03). Subjects with either heterozygous(GA)/minor(AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls(OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls(P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found(P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls(P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. T h e average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.展开更多
PTPN22 has been previously found associated with coronary artery disease(CAD). In the present note we have studied the effect of p53 codon 72,acid phosphatse locus 1(ACP1) and adenosine deaminase(ADA) genetic polymorp...PTPN22 has been previously found associated with coronary artery disease(CAD). In the present note we have studied the effect of p53 codon 72,acid phosphatse locus 1(ACP1) and adenosine deaminase(ADA) genetic polymorphism on the strength of association between PTPN22 and CAD. We have studied 133 non diabetic subjects with CAD,122 non diabetic cardiovascular patients without CAD and 269 healthy blood donors. Informed written consent was obtained from all subjects and the study was approved by the Ethical Committee. A high significant association between PTPN22 and CAD is observed in carriers of *A allele of ACP1 with a higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to controls and to non diabetic subjects with cardiovascular diseasewithout CAD. A similar pattern is observed in carriers of *Pro allele of p53 codon 72 with a higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to other groups. A highly significant association between PTPN22 and CAD is observed in carriers of ADA2 *2 allele with higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to other group. There is a high significant correlation between the number of factors that contributes to increase the strength of association between PTPN22 *T and CAD and the proportion of *T carriers in CAD. ACP1,p53 codon 72 and ADA are involved in immune reaction and give an important additive contribution to the strength of association between PTPN22 and CAD. This study stresses the importance of the simultaneous analysis of multiple genes functionally related to a specific disease: the approach may give important hints to understand multifactorial disorders.展开更多
PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first ident...PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.展开更多
基金Supported by the Florida Legislative Grant and the Crohn’s Disease Grant Funded by the State of Florida(in part)
文摘AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms(SNPs) in PTPN2/22 using TaqMan^(?) genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis(MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin(PHA) mitogen or mycobacterial antigens by Brd U proliferation assays for T-cell activity. RESULTS Out of the nine SNPs examined, subjects with either heterozygous(TC)/minor(CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls(P-values < 0.05; OR = 3.03). Subjects with either heterozygous(GA)/minor(AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls(OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls(P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found(P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls(P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. T h e average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.
文摘PTPN22 has been previously found associated with coronary artery disease(CAD). In the present note we have studied the effect of p53 codon 72,acid phosphatse locus 1(ACP1) and adenosine deaminase(ADA) genetic polymorphism on the strength of association between PTPN22 and CAD. We have studied 133 non diabetic subjects with CAD,122 non diabetic cardiovascular patients without CAD and 269 healthy blood donors. Informed written consent was obtained from all subjects and the study was approved by the Ethical Committee. A high significant association between PTPN22 and CAD is observed in carriers of *A allele of ACP1 with a higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to controls and to non diabetic subjects with cardiovascular diseasewithout CAD. A similar pattern is observed in carriers of *Pro allele of p53 codon 72 with a higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to other groups. A highly significant association between PTPN22 and CAD is observed in carriers of ADA2 *2 allele with higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to other group. There is a high significant correlation between the number of factors that contributes to increase the strength of association between PTPN22 *T and CAD and the proportion of *T carriers in CAD. ACP1,p53 codon 72 and ADA are involved in immune reaction and give an important additive contribution to the strength of association between PTPN22 and CAD. This study stresses the importance of the simultaneous analysis of multiple genes functionally related to a specific disease: the approach may give important hints to understand multifactorial disorders.
基金funded by NIH grants R01DK075916 and R01HL096125supported by Chinese National Key Project(2012ZX10002-009,011,013)+2 种基金National Natural Science Foundation of China(Grant Nos.30921006,30900770)Key Basic Science Foundation of Shanghai(10JC1418500)Project of the State Key Laboratory of Shanghai Jiaotong University(91-10-02).
文摘PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.
