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首页> 外文期刊>Biochemical Genetics >Polymorphism and Expression Profile of Cholecystokinin Type A Receptor in Relation to Gallstone Disease Susceptibility
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Polymorphism and Expression Profile of Cholecystokinin Type A Receptor in Relation to Gallstone Disease Susceptibility

机译:胆囊收缩素A型受体的多态性和表达谱与胆结石易感性的关系

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摘要

In the present study, we investigated expression pattern of Cholecystokinin type A receptor (CCKAR) in relation to its commonly studied polymorphism (rs1800857, T/C) in gallstone disease (GSD) patients and controls. A total of 502 subjects (272 GSD and 230 controls) were enrolled, and genotyping was performed by evaluating restriction fragments of PstI digested DNA. For analyzing expression pattern of CCKAR in relation to polymorphism, gallbladder tissue samples from 80 subjects (GSD-55; control-25) were studied. Expression of CCKAR mRNA was evaluated by reverse transcriptase-PCR and confirmed using real-time PCR. Protein expression was evaluated by enzyme-linked immunosorbent assay. We observed significantly (p < 0.0001) lower expression of CCKAR mRNA and protein in GSD tissues as compared with control. Significantly higher frequency of A1/A1 genotype (C/T transition) (p = 0.0005) was observed for GSD as compared with control. Expression of CCKAR protein was found to be significantly lower (p < 0.0001) in A1/A1 genotype as compared with other genotypes for GSD patients. Perhaps, this is the first report providing evidence of alteration in CCKAR expression in relation to its polymorphism elucidating the molecular pathway of the disease. Additional investigations with lager sample size are needed to confirm these findings.
机译:在本研究中,我们研究了胆囊收缩素A型受体(CCKAR)在胆结石病(GSD)患者和对照中与其通常研究的多态性(rs1800857,T / C)相关的表达模式。共有502名受试者(272名GSD和230名对照)参加,通过评估PstI消化的DNA的限制性片段进行基因分型。为了分析与多态性相关的CCKAR表达模式,研究了来自80名受试者(GSD-55;对照-25)的胆囊组织样品。通过逆转录PCR-PCR评估CCKAR mRNA的表达,并使用实时PCR确认。通过酶联免疫吸附测定法评估蛋白质表达。与对照组相比,我们观察到GSD组织中CCKAR mRNA和蛋白的表达显着降低(p <0.0001)。与对照相比,对于GSD,观察到A1 / A1基因型(C / T转变)的频率更高(p = 0.0005)。与GSD患者的其他基因型相比,在A1 / A1基因型中CCKAR蛋白的表达明显降低(p <0.0001)。也许,这是第一份报告,该报告提供了与CCKAR表达多态性有关的证据,阐明了该疾病的分子途径。需要更多样本量的额外调查来证实这些发现。

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