Gloria-Bottini Fulvia, Saccucci Patrizia, Banci Maria, Nardi Paolo, Scognamiglio Mattia, Pellegrino Antonio, Bottini Egidio, Chiariello Luigi
Fulvia Gloria-Bottini, Patrizia Saccucci, Egidio Bottini, Department of Biomedicine and Prevention, School of Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
World J Cardiol. 2014 Jun 26;6(6):376-80. doi: 10.4330/wjc.v6.i6.376.
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 disease without 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.
此前已发现蛋白酪氨酸磷酸酶非受体型22（PTPN22）与冠状动脉疾病（CAD）有关。在本报告中，我们研究了p53密码子72、酸性磷酸酶基因座1（ACP1）和腺苷脱氨酶（ADA）基因多态性对PTPN22与CAD之间关联强度的影响。我们研究了133例患有CAD的非糖尿病患者、122例无CAD的非糖尿病心血管疾病患者以及269名健康献血者。所有受试者均签署了知情书面同意书，本研究获得了伦理委员会的批准。在ACP1的A等位基因携带者中，观察到PTPN22与CAD之间存在高度显著的关联，与对照组以及无CAD的非糖尿病心血管疾病患者相比，患有CAD的非糖尿病患者中T等位基因携带者的比例更高。在p53密码子72的Pro等位基因携带者中也观察到类似模式，与其他组相比，患有CAD的非糖尿病患者中T等位基因携带者的比例更高。在ADA2 2等位基因携带者中，观察到PTPN22与CAD之间存在高度显著的关联，与其他组相比，患有CAD的非糖尿病患者中T等位基因携带者的比例更高。导致PTPN22 T与CAD之间关联强度增加的因素数量与CAD中T携带者的比例之间存在高度显著的相关性。ACP1、p53密码子72和ADA参与免疫反应，并对PTPN22与CAD之间的关联强度产生重要的累加作用。本研究强调了同时分析与特定疾病功能相关的多个基因的重要性：这种方法可能为理解多因素疾病提供重要线索。
