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
p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine（Arg） to a proline（Pro） at codon 72 can influence the biological activity ...p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine（Arg） to a proline（Pro） at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion（RSA）. In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio（OR） with 95% confidence interval（CI） was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium（HWE）. There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model（Pro/Pro vs. Pro/Arg＋Arg/Arg; OR=1.60, 95% CI： 1.14–2.24） and co-dominant model（Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI： 1.02–2.12） whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model（Pro vs. Arg; OR=1.28, 95% CI： 1.04–1.57） after exclusion of the study that was deviated from HWE. No association was noted in recessive model（Pro/Pro＋Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI： 0.86–1.30） and co-dominant model（Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI： 0.77–1.19）. Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA.展开更多
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supported by The National Science and Technology Pillar of China program during the Twelfth Five-Year Plan Period(No.2014BAI 05B05)
文摘p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine（Arg） to a proline（Pro） at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion（RSA）. In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio（OR） with 95% confidence interval（CI） was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium（HWE）. There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model（Pro/Pro vs. Pro/Arg＋Arg/Arg; OR=1.60, 95% CI： 1.14–2.24） and co-dominant model（Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI： 1.02–2.12） whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model（Pro vs. Arg; OR=1.28, 95% CI： 1.04–1.57） after exclusion of the study that was deviated from HWE. No association was noted in recessive model（Pro/Pro＋Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI： 0.86–1.30） and co-dominant model（Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI： 0.77–1.19）. Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA.
