本文選題：AKR1C3　切入點(diǎn)：單核苷酸多態(tài)性　出處：《福建醫(yī)科大學(xué)》2016年碩士論文

【摘要】：【背景】醛-酮還原酶(AKR)是氧化還原酶超家族的成員之一。它包含16個(gè)家族,約190個(gè)成員,廣泛存在于各類生物體中。AKR1C3是醛酮還原酶第一個(gè)家族的C3成員。人類AKR1C3基因編碼NADPH依賴型氧化還原酶,并催化醛酮化合物等致癌物質(zhì)還原成相應(yīng)的無毒或低毒的醇類,從而保護(hù)細(xì)胞不受損害。人AKR1C3基因具有高度多態(tài)性,這主要是因?yàn)锳KR1C3基因中存在多個(gè)單核苷酸多態(tài)性(SNPs),AKR1C3基因多個(gè)位點(diǎn)的單核苷酸突變導(dǎo)致的其編碼肽鏈氨基酸序列發(fā)生改變,從而影響酶蛋白結(jié)構(gòu)及其催化解毒作用,而影響癌癥易感性。既往研究表明AKR1C3基因單核苷酸多態(tài)性與腫瘤的發(fā)生和發(fā)展相關(guān)。目前國內(nèi)外已經(jīng)已有多項(xiàng)關(guān)于AKR1C3基因單核苷酸多態(tài)性與癌癥易感性關(guān)聯(lián)的研究,但是研究結(jié)果并不完全一致,因此我們進(jìn)行這一Meta分析來綜合地評(píng)估AKR1C3基因單核苷酸多態(tài)性與癌癥易感性的相關(guān)性。【方法】檢索PubMed、EMbase、OVID、CMB(中國生物醫(yī)學(xué)數(shù)據(jù)庫)和Cochrane library數(shù)據(jù)庫。收集有關(guān)AKR1C3基因單核苷酸多態(tài)性與癌癥易感性關(guān)系的文獻(xiàn),剔除不符合要求的文獻(xiàn)。并根據(jù)異質(zhì)性檢驗(yàn)結(jié)果選擇固定效應(yīng)模型和隨機(jī)效應(yīng)模型進(jìn)行數(shù)據(jù)合并分析。然后計(jì)算合計(jì)的比值比(OR)及95%可信區(qū)間來評(píng)估AKR1C3基因單核苷酸多態(tài)性與癌癥相關(guān)性,并通過亞組分析探討異質(zhì)性來源,運(yùn)用漏斗圖評(píng)估發(fā)表偏倚,敏感性分析檢驗(yàn)結(jié)果穩(wěn)定性�！窘Y(jié)果】本研究共納入12篇文獻(xiàn),其中關(guān)于rs12529位點(diǎn)的8篇,關(guān)于rs4881400位點(diǎn)的3篇,關(guān)于rs2245191位點(diǎn)的4篇,關(guān)于rs3763676位點(diǎn)的3篇,以及關(guān)于rs12387位點(diǎn)的3篇,分析結(jié)果顯示AKR1C3基因rs12529位點(diǎn)的單核苷酸多態(tài)性與癌癥的易感性無顯著關(guān)聯(lián),但亞組分析發(fā)現(xiàn)在亞洲人群中rs12529位點(diǎn)單核苷酸多態(tài)性在以下基因模型(等位基因模型G vs C,OR=1.64,95%CI 1.13 2.38,P=0.009;顯性基因模型CG+GG vs CC,OR=1.78,95%CI 1.03 3.07,P=0.04)與癌癥易感性明顯相關(guān)。此外本研究還發(fā)現(xiàn)攜帶rs3763676位點(diǎn)GA或GG基因型個(gè)體相對(duì)AA基因型個(gè)體存在更高的癌癥風(fēng)險(xiǎn)(顯性基因模型GA+GG vs AA,OR=1.20,95%CI 1.03 1.40,P=0.02)。關(guān)于人AKR1C3 rs4881400、rs2245191和rs12387位點(diǎn)單核苷酸多態(tài)性分析結(jié)果,沒有發(fā)現(xiàn)其與癌癥易感性相關(guān)。【結(jié)論】人AKR1C3基因rs12529位點(diǎn)多態(tài)性可能與亞洲人癌癥的易感性相關(guān),攜帶G等位基因可能是癌癥的危險(xiǎn)因素。且發(fā)現(xiàn)攜帶AKR1C3基因rs3763676位點(diǎn)GA或GG基因型個(gè)體相對(duì)AA基因型個(gè)體其癌癥易感性增高。AKR1C3基因rs4881400、rs2245191和rs12387位點(diǎn)不影響癌癥的易感性。但上述結(jié)果仍需要更多大樣本及高質(zhì)量的研究來證實(shí)。
[Abstract]:Background: aldehyde-ketone reductase (AKR) is a member of the superfamily of redox enzymes.It consists of 16 families with about 190 members. AKR1C3 is the first C3 member of aldehydes and ketones reductase.Human AKR1C3 gene encodes NADPH dependent redox reductase and catalyzes the reduction of carcinogens such as aldehydes and ketones to corresponding nontoxic or low toxic alcohols so as to protect cells from damage.Human AKR1C3 gene is highly polymorphic, which is mainly due to the change of amino acid sequence of encoding peptide chain caused by multiple single nucleotide mutations in AKR1C3 gene.Thus affecting the enzyme protein structure and catalytic detoxification, and affect cancer susceptibility.Previous studies have shown that the single nucleotide polymorphism of AKR1C3 gene is associated with the occurrence and development of tumor.Therefore, we conducted this Meta analysis to evaluate the association between single nucleotide polymorphisms of AKR1C3 gene and cancer susceptibility. [methods] PubMedbase OVIDB (Chinese Biomedical Database) and Cochrane library database were searched.To collect the literature about the relationship between AKR1C3 gene single nucleotide polymorphism and cancer susceptibility, and eliminate the non-conforming literature.According to the results of heterogeneity test, fixed effect model and random effect model are selected for data merging analysis.Then we calculated the ratio ratio (ORR) and 95% confidence interval to evaluate the association between AKR1C3 gene single nucleotide polymorphism and cancer, and used subgroup analysis to explore the source of heterogeneity, and to use funnel graph to evaluate publication bias.[results] A total of 12 articles were included in this study, including 8 articles on rs12529 loci, 3 on rs4881400 loci, 4 on rs2245191 loci, 3 on rs3763676 loci, and 3 on rs12387 loci.The results showed that there was no significant association between the single nucleotide polymorphisms at rs12529 locus of AKR1C3 gene and the susceptibility to cancer.In addition, it was also found that individuals with rs3763676 locus GA or GG genotype had a higher cancer risk than AA genotype individuals (dominant gene model GA GG vs AA GG 1.20 95 / 1.03 CI 1.40 P0. 02).The results of single nucleotide polymorphism analysis of human AKR1C3 rs4881400 rs2245191 and rs12387 locus showed no association with cancer susceptibility. [conclusion] the polymorphism of rs12529 locus of human AKR1C3 gene may be associated with cancer susceptibility in Asian people.Carrying the G allele may be a risk factor for cancer.It was also found that the individuals carrying rs3763676 locus of AKR1C3 gene GA or GG genotype were more susceptible to cancer than those of AA genotype. Rs4881400 rs2245191 and rs12387 locus of AKR1C3 gene did not affect the susceptibility to cancer.But these results still need more large samples and high-quality research to confirm.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R730.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前2條

1 甄明慧;杜英;馮國清;朱沙;;AKR1C3基因沉默對(duì)前列腺癌PC3細(xì)胞轉(zhuǎn)移潛能及多西紫杉醇敏感性影響研究[J];中華腫瘤防治雜志;2014年04期

2 ;[J];;年期

相關(guān)碩士學(xué)位論文 前1條

1 林永信;人AKR1C3基因多態(tài)性與癌癥易感性關(guān)聯(lián)的Meta分析[D];福建醫(yī)科大學(xué);2016年

，

本文編號(hào)：1696213