本文關(guān)鍵詞：新疆維吾爾族HLA-Ⅱ類基因多態(tài)性與HPV感染、宮頸病變及宮頸癌的關(guān)系研究　出處：《新疆醫(yī)科大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 維吾爾族 宮頸上皮內(nèi)瘤變 子宮頸癌 高危型人乳頭狀瘤病毒感染 人類白細(xì)胞抗原-Ⅱ類等位基因多態(tài)性 導(dǎo)流雜交基因芯片技術(shù) 聚合酶鏈反應(yīng)序列寡核苷酸探針雜交法 直接測(cè)序分型

【摘要】：目的:探討HLA-DRB1、DQB1等位基因多態(tài)性及HLA-DRB1和HLA-DQB1的單倍體型與新疆維吾爾族HPV、HPV16感染及宮頸癌發(fā)生、發(fā)展的關(guān)系,通過(guò)遺傳易感性方面研究新疆維吾爾族宮頸癌的病因及發(fā)生機(jī)制,為今后易感人群的篩查及監(jiān)測(cè)提供理論依據(jù)。研究方法:1)采用人乳頭狀瘤病毒(HPV)基因微陣列分型檢測(cè)試劑盒,以凱普醫(yī)用核酸分子快速雜交儀為平臺(tái),利用導(dǎo)流雜交原理,已經(jīng)固定好核酸探針的低密度基因芯片膜上,快速對(duì)370例明確診斷宮頸癌和同一地區(qū)匹配的370例健康對(duì)照以及117例CIN患者血液中檢測(cè)21種HPV亞型(包括13種HPV高危亞型;5種HPV低危亞型;3種中國(guó)人群常見(jiàn)HPV亞型);2)采用聚合酶鏈?zhǔn)椒磻?yīng)結(jié)合直接測(cè)序分型(polymerase chain reaction-sequence-based typing,PCR-SBT)法,對(duì)370例明確診斷宮頸癌和同一地區(qū)匹配的370例健康對(duì)照以及117例CIN患者血液中進(jìn)行HLA-DRB1等位基因的檢測(cè),并比較各等位基因在研究對(duì)象中的分布頻率;3)采用聚合酶鏈反應(yīng)序列特異性寡核苷酸探針(Polymerase chain reaction sequence-specific oligonucleotide,PCR-SSO)法,對(duì)200例明確診斷宮頸癌和同一地區(qū)匹配的200例健康對(duì)照血液中進(jìn)行HLA-DQB1等位基因的檢測(cè),并比較各等位基因在研究對(duì)象中的分布頻率;4)從全疆HLA-DRB1檢測(cè)結(jié)果中,挑選來(lái)自南疆宮頸癌患者共200例,健康對(duì)照共200例的HLA-DRB1等位基因數(shù)據(jù),利用HLA-DQB1數(shù)據(jù),分析HLA-DRB1-DQB1單倍體在研究對(duì)象中的分布頻率;結(jié)果:一:HPV及其亞型分布情況:1)全疆研究對(duì)象中,宮頸癌組共370例,其中HPV陽(yáng)性共322例,HPV陽(yáng)性率為87.0%(322/370)。CIN組共117例,其中HPV陽(yáng)性共95例,HPV陽(yáng)性率為81.2%(95/117)。HPV各亞型共出現(xiàn)481次,HPV16感染所占的比例最高74.8%(360/481)。宮頸癌組中,HPV16陽(yáng)性率為72.7%(269/370)。2)南疆研究對(duì)象中,宮頸癌組共200例,其中HPV陽(yáng)性共179例,HPV陽(yáng)性率為89.5%(179/200)。HPV各亞型共出現(xiàn)219次,HPV16感染所占的比例最高80.4%(176/219),HPV16陽(yáng)性率為81.0%(162/200)。二、HLA-DRB1在HPV和HPV16型感染、宮頸癌中分布情況如下:1)統(tǒng)計(jì)發(fā)現(xiàn)HLA-DRB1*15等位基因在HPV(+)/HPV16(+)組中出現(xiàn)的頻率高于HPV(-)/HPV16(-)組,差異有統(tǒng)計(jì)學(xué)意義(χ2=11.371,P=0.001,OR=1.670,95%CI=1.237-2.254;χ2=7.778,P=0.005,OR=2.782,95%CI=1.318-5.872)。HLA-DRB1*15等位基因在宮頸癌組出現(xiàn)頻率為14.2%,CIN組出現(xiàn)頻率為13.2%,對(duì)照組出現(xiàn)頻率為9.9%,出現(xiàn)頻率在三組之間有差異,差異有統(tǒng)計(jì)學(xué)意義(χ2=6.743,P=0.034)。HLA-DRB1*15等位基因在宮頸癌組和病例組中出現(xiàn)的頻率高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(χ2=6.539,P=0.011,OR=1.511,95%CI=1.099-2.076;χ2=6.596,P=0.010,OR=1.483,95%CI=1.096-2.006)。2)HLA-DRB1*12等位基因在HPV(+)組中出現(xiàn)的頻率低于HPV(-)組,差異有統(tǒng)計(jì)學(xué)意義(χ2=8.137,P=0.004,OR=0.441,95%CI=0.248-0.785)。HLA-DRB1*12者在病例組中出現(xiàn)的頻率低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(χ2=4.021,P=0.045,OR=0.572,95%CI=0.330-0.994)。3)在HPV16感染的研究對(duì)象中,HLA-DRB1*13基因在宮頸癌組、CIN組及對(duì)照組中頻率之間有差異,差異有統(tǒng)計(jì)學(xué)意義(χ2=9.759,P=0.008)。并且HLA-DRB1*13者在宮頸癌組和病例組中出現(xiàn)的頻率低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(χ2=9.704,P=0.002,OR=0.313,95%CI=0.145-0.673;χ2=9.668,P=0.002,OR=0.320,95%CI=0.151-0.679)。三、HLA-DQB1在HPV和HPV16型感染、宮頸癌中分布情況如下:1)HLA-DQB1*06者在HPV陽(yáng)性組中出現(xiàn)的頻率高于HPV陰性組,差異有統(tǒng)計(jì)學(xué)意義(χ2=6.578,P=0.010,OR=1.572,95%CI=1.111-2.223)。HLA-DQB1*06等位基因在HPV16(+)組中出現(xiàn)頻率高于HPV16(-)組,差異有統(tǒng)計(jì)學(xué)意義(χ2=4.272,P=0.039,OR=2.368,95%CI=1.024-5.479),說(shuō)明攜帶HLA-DQB1*06等位基因的維吾爾族婦女更容易被HPV16感染2)而HLA-DQB1*03等位基因在HPV陽(yáng)性組中出現(xiàn)的頻率低于HPV陰性組,差異有統(tǒng)計(jì)學(xué)意義(χ2=7.930,P=0.005,OR=0.654,95%CI=0.487-0.880)。HLA-DQB1*03等位基因在宮頸癌組中出現(xiàn)的頻率低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(χ2=8.519,P=0.004,OR=0.645,95%CI=0.480-0.866)。。四、HLA-DRB1和DQB1單倍型在HPV和HPV16型感染、宮頸癌中分布情況如下:1)HLA-DRB1*15和HLA-DQB1*06單倍型在HPV陽(yáng)性組中出現(xiàn)的頻率高于HPV陰性組,差異有統(tǒng)計(jì)學(xué)意義(χ2=9.558,P=0.002,OR=2.088,95%CI=1.299-3.356)。HLA-DRB1*15和HLA-DQB1*06單倍型在宮頸癌組中出現(xiàn)的頻率高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(χ2=8.402,P=0.004,OR=1.997,95%CI=1.242-3.209)。2)而HLA-DRB1*04和HLA-DQB1*03單倍型在宮頸癌組中出現(xiàn)的頻率低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(χ2=4.228,P=0.040,OR=0.584,95%CI=0.348-0.980)。結(jié)論:一、1.全疆和南疆維吾爾族婦女宮頸癌患者主要以HPV16感染為主;二、HLA-DRB1:1)HLA-DRB1*15等位基因可能是維吾爾族HPV、HPV16感染的易感基因。HLA-DRB1*15等位基因基因可能由非宮頸病變到癌前病變發(fā)展至宮頸癌過(guò)程中的易感基因。同時(shí)HLA-DRB1*15等位基因基因可能是維吾爾族提高CIN以上病變和宮頸癌的易感基因。2)HLA-DRB1*12等位基因可能是維吾爾族HPV感染和CIN以上病變的保護(hù)基因,3)在HPV16型感染的研究對(duì)象中,HLA-DRB1*13等位基因可能由非宮頸病變到癌前病變發(fā)展至宮頸癌過(guò)程中的保護(hù)基因。HLA-DRB1*13基因可能是CIN以上病變和宮頸癌的保護(hù)基因。三:HLA-DQB1:1)HLA-DQB1*06基因可能是維吾爾族婦女HPV及HPV16感染的易感基因。2)HLA-DQB1*03基因可能是維吾爾族HPV感染和宮頸癌的保護(hù)基因。四:HLA-DRB1和DQB1單倍體:1)HLA-DRB1*15和HLA-DQB1*06單倍型可能是HPV感染和宮頸癌的易感基因。2)HLA-DRB1*04和HLA-DQB1*03單倍型可能是宮頸癌的保護(hù)基因。
[Abstract]:Objective: To investigate the HLA-DRB1, DQB1 and HLA-DRB1 alleles polymorphism and HLA-DQB1 haplotype and Xinjiang Uygur HPV, HPV16 infection and cervical cancer occurrence and development relations, through the study of genetic susceptibility in Xinjiang Uygur etiology and pathogenesis of cervical carcinoma, and provide a theoretical basis for screening and monitoring in susceptible populations. Research methods: 1) the human papilloma virus (HPV) gene microarray genotyping kit, with Cape rapid acid hybridization medical instrument platform, using flow-through hybridization principle, low density gene chip film has been fixed on the nucleic acid probe, 370 cases were diagnosed on rapid detection of 21 subtypes of HPV in healthy control 370 cases of cervical cancer and the same area, and 117 cases of CIN in the blood of patients (including 13 high-risk subtypes of HPV; 5 HPV low-risk subtypes; 3 people Chinese common subtype HPV); 2) polymerase chain The reaction combined with direct sequencing typing (polymerase chain reaction-sequence-based typing, PCR-SBT), 370 patients diagnosed by detection of HLA-DRB1 alleles and 370 healthy control cases of cervical cancer and the same area, and 117 cases of CIN in the blood of patients, and compare the frequency distribution of alleles in the study group; 3) polymerase chain reaction sequence specific oligonucleotide probes (Polymerase chain reaction sequence-specific oligonucleotide, PCR-SSO), 200 patients with definite diagnosis of cervical cancer and the same area, 200 cases of healthy controls were detected the HLA-DQB1 allele in the blood, and compare the frequency distribution of the alleles in the study group; 4) from Xinjiang HLA-DRB1 test results, selected from the southern cervical cancer patients with a total of 200 cases of healthy control were 200 cases of allele HLA-DRB1 data, using HLA-DQB1 data points 鏋怘LA-DRB1-DQB1鍗曞，

本文編號(hào)：1424827