Safranow Krzysztof, Rzeuski Ryszard, Binczak-Kuleta Agnieszka, Czyzycka Edyta, Skowronek Janusz, Jakubowska Katarzyna, Wojtarowicz Andrzej, Loniewska Beata, Ciechanowicz Andrzej, Kornacewicz-Jach Zdzislawa, Chlubek Dariusz
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
Cardiology. 2007;108(4):275-81. doi: 10.1159/000099096. Epub 2007 Feb 8.
BACKGROUND/AIMS: The common G22A polymorphism in the adenosine deaminase (ADA) gene leads to substitution Asp8Asn. The lower activity of the enzyme encoded by A22 (ADA*2) allele may increase tissue concentrations of adenosine, a potent cardioprotective agent. In a case-control study, we investigated the association between ADA polymorphism and coronary artery disease (CAD).
A hundred and seventy-one CAD patients from the north-western part of Poland and 200 consecutive newborns from the same population were genotyped by PCR-RFLP.
Twenty-five ADA*1/2 heterozygotes (12.5%) and 2 ADA2/*2 homozygotes (1%) were found in the control group, while only 10 *1/*2 heterozygotes (5.9%) and no 2/2 homozygotes were found in the CAD group. Frequencies of ADA2 carriers (5.9% vs. 13.5%, p = 0.015) and ADA2 allele (2.9% vs. 7.3%, p = 0.0083) were lower in CAD patients than in controls. Among CAD patients, a significantly lower proportion of *2 allele carriers was treated with diuretics and ACE inhibitors when compared to *1/*1 wild-type homozygotes.
ADA*2 allele may decrease genetic susceptibility to CAD. ADA should be added to the list of candidate genes modifying the risk of cardiovascular diseases.
背景/目的:腺苷脱氨酶(ADA)基因常见的G22A多态性导致天冬氨酸8被天冬酰胺取代。由A22(ADA*2)等位基因编码的酶活性较低,可能会增加组织中腺苷的浓度,腺苷是一种有效的心脏保护剂。在一项病例对照研究中,我们调查了ADA多态性与冠状动脉疾病(CAD)之间的关联。
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对来自波兰西北部的171例CAD患者和来自同一人群的200例连续新生儿进行基因分型。
在对照组中发现25例ADA1/2杂合子(12.5%)和2例ADA2/2纯合子(1%),而在CAD组中仅发现10例1/2杂合子(5.9%),未发现2/2纯合子。CAD患者中ADA2携带者的频率(5.9%对13.5%,p = 0.015)和ADA2等位基因的频率(2.9%对7.3%,p = 0.0083)低于对照组。在CAD患者中,与*1/*1野生型纯合子相比,*2等位基因携带者接受利尿剂和血管紧张素转换酶抑制剂治疗的比例显著较低。
ADA*2等位基因可能会降低CAD的遗传易感性。ADA应被列入影响心血管疾病风险的候选基因名单中。