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hTERT基因多態(tài)性與宮頸癌前病變的關(guān)聯(lián)性研究

發(fā)布時間:2019-05-22 11:22
【摘要】:[目的]探討人端粒酶逆轉(zhuǎn)錄酶(hTERT)基因單核苷酸多態(tài)性與宮頸癌前病變發(fā)生發(fā)展的相關(guān)性。[方法]選取2015年1月至2016年9月在昆明醫(yī)科大學(xué)第三附屬醫(yī)院婦科門診體檢及婦科住院患者為本研究對象,其中高危型HPV感染陰性、無宮頸病變的健康女性共200例為對照組;病理確診宮頸癌前病變患者300例為實驗組。收集宮頸癌前病變患者的宮頸組織以及對照組人群的外周血,提取標(biāo)本的DNA,采用TaqMan探針基因分型方法,對hTERT基因的4個SNP位點rs2736122 (G A),rs2853676 (CT) , rs2853677 (AG),rs2075786 (AG)進(jìn)行基因測序,并構(gòu)建單倍型,計算各SNP位點等位基因、基因型、單倍型在實驗組與對照組之間、不同級別宮頸鱗狀上皮內(nèi)病變之間的頻率和差異,探討各位點等位基因、基因型、單倍型頻率與宮頸癌前病變發(fā)生發(fā)展的相關(guān)性。[結(jié)果]1.Hardy-Weinberg平衡檢驗結(jié)果表明,hTERT基因4個SNP位點在實驗組與對照組中的基因型分布全部符合Hardy-Weinberg平衡(P0.05),提示本實驗所用樣本具有群體代表性。2.hTERT基因的4個SNP位點基因測序結(jié)果顯示,實驗組、對照組間4個SNP位點rs2736122(GA),rs2853676(CT), rs2853677(AG), rs2075786(AG)的基因型頻率、等位基因頻率比較,差異均無統(tǒng)計學(xué)意義,P0.05。3.連鎖不平衡分析結(jié)果顯示:在4個組內(nèi),rs2075786 (AG)與rs2736122(GA)間存在較強的連鎖不平衡關(guān)系,D'0.8;其余各組間關(guān)聯(lián)不明顯,D'0.8。4.根據(jù)連鎖不平衡分析結(jié)果構(gòu)建hTERT基因rs2075786/rs2736122的單倍型,結(jié)果表明A-G、G-A和G-G 3種單倍型頻率分布在宮頸癌前病變組與健康對照組之間、不同級別宮頸鱗狀上皮內(nèi)病變組之間差異無統(tǒng)計學(xué)意義,P0.05。5.對低級別與高級別宮頸鱗狀上皮內(nèi)病變之間進(jìn)行hTERT基因4個SNP位點基因型頻率、等位基因頻率的比較,結(jié)果顯示:rs2736122 (GA)、rs2853676(CT)、rs2075786 (AG)單位點低級別宮頸鱗狀上皮內(nèi)病變組和高級別宮頸鱗狀上皮內(nèi)病變組比較等位基因和基因型頻率差異無統(tǒng)計學(xué)意義,P0.05。rs2853677 (AG)位點,低級別宮頸鱗狀上皮內(nèi)病變組和高級別宮頸鱗狀上皮內(nèi)病變組比較等位基因頻率差異無統(tǒng)計學(xué)意義,P值為0.330;但兩組比較基因型頻率差異具有統(tǒng)計學(xué)意義,P值為0.012。6.遺傳模式分析結(jié)果顯示:hTERT基因rs2853677 (AG)位點,超顯性遺傳模式可能為該位點的最佳遺傳模式;在超顯性遺傳模式中,把基因型A/A+G/G作為參考,基因型A/G在低級別宮頸鱗狀上皮內(nèi)病變組和高級別宮頸鱗狀上皮內(nèi)病變組中的比較P=:2×104, OR=2.83, 95%CI=1.61~4.99,差異有統(tǒng)計學(xué)意義,P0.05, AG基因型增加了低級別宮頸鱗狀上皮內(nèi)病變進(jìn)一步發(fā)展為高級別宮頸鱗狀上皮內(nèi)病變的風(fēng)險。[結(jié)論]1.hTERT基因 SNP 位點 rs2736122 (GA) , rs2853676 (C T),rs2075786(AG)多態(tài)性與宮頸癌前病變發(fā)生發(fā)展危險性無明顯相關(guān)性。.2.hTERT基因SNP位點rs2853677 (AG)多態(tài)性與宮頸癌前病變發(fā)病風(fēng)險性無明顯相關(guān)性,但與宮頸癌前病變的發(fā)展存在相關(guān)性,A/G基因型可能增加了低級別宮頸鱗狀上皮內(nèi)病變進(jìn)一步發(fā)展為高級別宮頸鱗狀上皮內(nèi)病變的風(fēng)險。3.hTERT基因rs2075786/rs2736122單倍型分布與宮頸癌前病變的發(fā)生發(fā)展無明顯相關(guān)性。
[Abstract]:[Objective] To study the relationship between the polymorphism of human telomerase reverse transcriptase (hTERT) gene and the development of precancerous lesion of cervical cancer. [Methods] A total of 200 healthy women with high-risk HPV infection and no cervical lesions were selected from January 2015 to September 2016 at the Third Affiliated Hospital of Kunming Medical University. In the first group,300 patients with premalignant cervical cancer were diagnosed as experimental group. and collecting the DNA of the specimen from the peripheral blood of the cervical tissue and the control group, collecting the DNA of the specimen, using the TaqMan probe gene typing method, performing gene sequencing on the four SNP loci rs2736122 (G A), rs2853676 (CT), rs2853677 (AG), rs2075786 (AG) of the hTERT gene, and constructing a haplotype, The frequency and difference of each SNP locus allele, genotype and haplotype between the experimental group and the control group and at different levels of the cervical squamous intraepithelial lesions were calculated. [Results] 1. The results of the Hardy-Weinberg equilibrium test showed that the genotype distribution of the four SNP sites of the hTERT gene in the experimental group and the control group was all in accordance with the Hardy-Weinberg equilibrium (P0.05). The genotypes of rs2736122 (GA), rs2853676 (CT), rs2853677 (AG) and rs2075786 (AG) in the control group were not statistically significant. The results of linkage disequilibrium analysis showed that in 4 groups, there was a strong linkage disequilibrium between rs2075786 (AG) and rs2736122 (GA), and D '0.8; the correlation between the other groups was not obvious, and D' 0.4.4. The haplotype of the hTERT gene rs2075786/ rs2736122 was constructed according to the results of the linkage disequilibrium analysis. The results showed that the single-fold frequency distribution of A-G, G-A and G-G was between the pre-cervical lesion and the healthy control group. The results showed that rs2736122 (GA), rs2853676 (CT), rs2736122 (GA), rs2853676 (CT), rs2075786 (ag) in the low-grade cervical squamous intraepithelial lesion group and the high-level cervical squamous intraepithelial lesion group, there was no significant difference in the allele and genotype frequency difference, p0.05 rs2853677 (ag) site, There was no significant difference in allele frequency among the lower-grade cervical squamous intraepithelial lesion group and the high-level cervical squamous intraepithelial lesion group, and the P value was 0.330; however, the frequency difference between the two groups was statistically significant and the P value was 0.012. The results of the genetic analysis showed that the gene of the hTERT gene rs2853677 (AG), the superdominant genetic pattern may be the best genetic model of the site, and in the superdominant genetic model, the genotype A/ A + G/ G was used as the reference. The P =:2-104, OR = 2.83,95% CI = 1.61-4.99 in the low-grade cervical squamous intraepithelial lesion group and the high-grade cervical squamous intraepithelial lesion group, the difference was statistically significant, P0.05, The AG genotype has increased the risk of further development of low-grade cervical squamous intraepithelial lesions to high-level cervical squamous intraepithelial lesions. [Conclusion] 1. The polymorphism of rs2736122 (GA), rs2853676 (C T) and rs2075786 (AG) of the hTERT gene is not related to the risk of the development of cervical cancer. 2. The rs2853677 (AG) polymorphism of the hTERT gene is not related to the risk of the premalignant lesion of cervical cancer, but there is a correlation with the development of the pre-cervical cancer. A/ G genotype may increase the risk of high-level cervical squamous intraepithelial lesions.3. The haplotype distribution of the hTERT gene rs2075786/ rs2736122 has no significant correlation with the development of pre-cervical lesions.
【學(xué)位授予單位】:昆明醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R737.33

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