van Oijen Martijn G H, Huybers Sylvie, Peters Wilbert H M, Drenth Joost P H, Laheij Robert J F, Verheugt Freek W A, Jansen Jan B M J
Department of Gastroenterology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Br J Clin Pharmacol. 2005 Dec;60(6):623-8. doi: 10.1111/j.1365-2125.2005.02495.x.
As acetylsalicylic acid is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9), interindividual differences in activity of these enzymes may modulate the effects and side-effects of acetylsalicylic acid. The objective of this study was to assess whether polymorphisms in UGT1A6 and CYP2C9 genes are related to the prevalence of upper gastrointestinal symptoms in cardiovascular patients using acetylsalicylic acid for secondary prevention of ischaemic heart disease.
Blood samples were taken from acetylsalicylic acid using patients admitted to the Coronary Care Unit. Dyspepsia-related health was evaluated at week 2, using a validated upper gastrointestinal complaint questionnaire. A subset of 160 patients responded to a survey and were eligible to participate in this study. DNA was isolated and UGT1A6 and CYP2C9 genotypes were determined using polymerase chain reaction restricted fragment length polymorphism techniques.
Seventy per cent of the patients returned the questionnaire. UGT1A6 and CYP2C9 variant polymorphisms were found in 103 (63%) and 56 (35%) patients, respectively. There was no association between gastrointestinal symptoms and UGT1A6 (OR = 0.80, 95% CI = 0.41-1.56) or CYP2C9 polymorphisms (OR = 0.85, 95% CI = 0.44-1.67).
There was no association between polymorphisms in genes encoding for acetylsalicylic acid metabolizing enzymes on the prevalence of gastric complaints in cardiovascular patients on acetylsalicylic acid.
由于乙酰水杨酸由尿苷二磷酸葡萄糖醛酸基转移酶1A6(UGT1A6)和细胞色素P450 2C9(CYP2C9)代谢,这些酶活性的个体差异可能会调节乙酰水杨酸的疗效和副作用。本研究的目的是评估UGT1A6和CYP2C9基因多态性是否与使用乙酰水杨酸进行缺血性心脏病二级预防的心血管疾病患者上消化道症状的发生率相关。
从入住冠心病监护病房且正在使用乙酰水杨酸的患者中采集血样。在第2周时,使用经过验证的上消化道症状问卷对消化不良相关健康状况进行评估。160名患者的一个子集对调查做出了回应并符合参与本研究的条件。分离DNA,并使用聚合酶链反应限制性片段长度多态性技术确定UGT1A6和CYP2C9基因型。
70%的患者返回了问卷。分别在103名(63%)和56名(35%)患者中发现了UGT1A6和CYP2C9变异多态性。胃肠道症状与UGT1A6(比值比=0.80,95%置信区间=0.41-1.56)或CYP2C9多态性(比值比=0.85,95%置信区间=0.44-1.67)之间无关联。
在使用乙酰水杨酸的心血管疾病患者中,编码乙酰水杨酸代谢酶的基因多态性与胃部不适的发生率之间无关联。