摘要
第一部分
50例吉林地区健康汉族人群和185例胃食管疾病患者CYP2C19基因多态性分析
目的:分析吉林地区健康汉族人群和胃食管疾病患者CYP2C19基因多态性。方法:50例无血缘关系的健康体检者参加本研究,其中男28例,女22例,年龄18~43岁,平均31.50±8.45岁。185例胃食管疾病患者。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法进行分析。结果:在50例健康汉族人中,弱代谢型共14例(14.00%),其中CYP2C19*2/CYP2C19*2型5例(10.00%),CYP2C19*2/ CYP2C19*3型2例(4.00%);强代谢型共43例(86.00%),其中外显子5及外显子4均为CYP2C19*1/CYP2C19*1型者19例,占38.00%;CYP2C19*1/CYP2C19*2型20例,占40.00%;CYP2C19*1/ CYP2C19*3型4例,占8.00%。由此,CYP2C19*1的等位基因频率为0.62(95%CI:0.56-0.68),CYP2C19*2的为0.32(95%CI: 0.26-0.38),CYP2C19*3的为0.06(95%CI:0.02-0.10)。食管癌组中CYP2C19弱代谢者5例,与健康组相比有显著性差异(P<0.05;OR:4.39, 95%CI:1.08-17.77)。结论:我国吉林地区健康汉族人群中,弱代谢型频率约为14.00%,其中CYP2C19*2占多数,其等位基因频率约为CYP2C19*3的5倍。CYP2C19*3等位基因的频率尽管相对较低,但它几乎说明了中国人剩余的全部弱代谢型等位基因。CYP2C19弱代谢型与
食管癌的发生具有显著相关性,CYP2C19弱代谢型增加了发生食管癌的相对危险性。
关键词 CYP2C19; PCR-RFLP; 基因多态性
第二部分
奥美拉唑治疗反流性食管炎的疗效及其与CYP2C19基因多态性关系的临床研究
目的:探讨短期应用奥美拉唑治疗反流性食管炎的疗效及其与CYP2C19基因多态性的关系。方法:应用奥美拉唑20mg每日晨起空腹口服一次,持续4周,治疗56例经胃镜证实的反流性食管炎患者。记录治疗前和用药2周后、4周后时症状的变化,并于治疗结束时复查胃镜。受试者 CYP2C19的基因型及幽门螺杆菌感染情况分别采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)及ELISA分析方法。结果:纯合子强代谢组、杂合子强代谢组和弱代谢组胃镜下治愈率分别为47.37%、69.23%和88.89%,纯合子强代谢组的治愈率显著低于弱代谢组(P<0.05)。性别差异并非影响反流性食管炎治愈率的主要因素。结论:CYP2C19基因多态性与奥美拉唑治疗反流性食管炎的疗效密切相关。CYP2C19基因分型检测是临床治疗酸相关性疾病中一个重要的工具。
Part I
Analysis of the CYP2C19 Polymorphism in 50 Chinese Han People and 185 Patients with Gastroesophageal Disease of JiLin Province
Objective: To assess the genotype pattern distribution of cytochrome P450 in Chinese Han population and patients with gastroesophageal disease of JiLin Province. Method: 50 unrelated healthy Chinese Han population subjects(28 males and 22 females, aged from 18~43) and 185 gastroesophageal disease patients were genotyped for CYP2C19 according to the polymerase chain reaction- restriction fragment length polymorphism technique(PCR-RFLP). Result: In 50 healthy people, 7 subjects (14.00%) were identified as poor metabolizers(PMs),consisting of 5 homozygous for CYP2C19*2/CYP2C19*2 and 2 heterozygous for CYP2C19*2/ CYP2C19*3,
there was no homozygous for CYP2C19*3/CYP2C19*3 being found. The frequency of extensive metabolizers(EMs) was 86.00% (43 of 50 subjects), consisting of 19(38.00%) homozygous for CYP2C19*1/ CYP2C19*1 in exon4 and exon5, 20(40.00%) heterozygous for CYP2C19*1/CYP2C19*2, 4(8.00%) heterozygous for CYP2C19*1/ CYP2C19*3. Thus allele frequencies for CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 0.62 [95% confidence interval (CI):0.56-0.68], 0.32 (95% CI:0.26-0.38) and 0.06(95%CI: 0.02-0.10), respectively. 5 CYP2C19 poor metabolizers were found in esophageal cancer patients, which showed a very significant difference than that of healthy controls. Conclusion: The frequency of poor metabolizers in Chinese is 14.00%, whereas the frequency of extensive metabolizers is 86.00%, CYP2C19*2 is the majority in two mutations and frequency of the CYP2C19*2 allele is about 5 times than that of mutant allele CYP2C19*3.These results are consistent with the exhibited reports. CYP2C19 poor metabolizers increase the risk of esophageal cancer significantly.
Key words CYP2C19; genetic polymorphism; PCR-RFLP
Part II
Association between CYP2C19 Polymorphism and the Effects of Omeprazole on Reflux Esophagitis
Objective: To investigate whether the CYP2C19 genotype is related to the healing of erosive reflux esophagitis during treatment with omeprazole. Method: Fifty-six Chinese patients with reflux esophagitis were treated with a daily oral dose of
20 mg omeprazole for 4 weeks. The CYP2C19 genotype, Helicobacter pylori infection status were assessed before treatment. At 4 weeks, the healing of reflux esophagitis was evaluated endoscopically. Result: The healing rates were 47.37%, 69.23% and 88.89% at 4 weeks in homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers, respectively. At 4 weeks, the healing rate of reflux esophagitis was significantly lower in homozygous extensive metabolizers than in poor metabolizers (P < 0.05). Sex had less influence than CYP2C19 polymorphism on the healing rate of reflux esophagitis. Conclusions: The therapeutic effect of omeprazole on reflux esophagitis is influenced by the CYP2C19 genotype status. Therefore, a test of CYP2C19 genotype may be useful for the medical treatment of reflux esophagitis with omeprazole.
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