hTERT基因多态性与宫颈癌前病变的关联性研究

发布时间：2019-05-22 11:22

【摘要】：[目的]探讨人端粒酶逆转录酶(hTERT)基因单核苷酸多态性与宫颈癌前病变发生发展的相关性。[方法]选取2015年1月至2016年9月在昆明医科大学第三附属医院妇科门诊体检及妇科住院患者为本研究对象,其中高危型HPV感染阴性、无宫颈病变的健康女性共200例为对照组;病理确诊宫颈癌前病变患者300例为实验组。收集宫颈癌前病变患者的宫颈组织以及对照组人群的外周血,提取标本的DNA,采用TaqMan探针基因分型方法,对hTERT基因的4个SNP位点rs2736122 (G A),rs2853676 (CT) , rs2853677 (AG),rs2075786 (AG)进行基因测序,并构建单倍型,计算各SNP位点等位基因、基因型、单倍型在实验组与对照组之间、不同级别宫颈鳞状上皮内病变之间的频率和差异,探讨各位点等位基因、基因型、单倍型频率与宫颈癌前病变发生发展的相关性。[结果]1.Hardy-Weinberg平衡检验结果表明,hTERT基因4个SNP位点在实验组与对照组中的基因型分布全部符合Hardy-Weinberg平衡(P0.05),提示本实验所用样本具有群体代表性。2.hTERT基因的4个SNP位点基因测序结果显示,实验组、对照组间4个SNP位点rs2736122(GA),rs2853676(CT), rs2853677(AG), rs2075786(AG)的基因型频率、等位基因频率比较,差异均无统计学意义,P0.05。3.连锁不平衡分析结果显示:在4个组内,rs2075786 (AG)与rs2736122(GA)间存在较强的连锁不平衡关系,D'0.8;其余各组间关联不明显,D'0.8。4.根据连锁不平衡分析结果构建hTERT基因rs2075786/rs2736122的单倍型,结果表明A-G、G-A和G-G 3种单倍型频率分布在宫颈癌前病变组与健康对照组之间、不同级别宫颈鳞状上皮内病变组之间差异无统计学意义,P0.05。5.对低级别与高级别宫颈鳞状上皮内病变之间进行hTERT基因4个SNP位点基因型频率、等位基因频率的比较,结果显示:rs2736122 (GA)、rs2853676(CT)、rs2075786 (AG)单位点低级别宫颈鳞状上皮内病变组和高级别宫颈鳞状上皮内病变组比较等位基因和基因型频率差异无统计学意义,P0.05。rs2853677 (AG)位点,低级别宫颈鳞状上皮内病变组和高级别宫颈鳞状上皮内病变组比较等位基因频率差异无统计学意义,P值为0.330;但两组比较基因型频率差异具有统计学意义,P值为0.012。6.遗传模式分析结果显示:hTERT基因rs2853677 (AG)位点,超显性遗传模式可能为该位点的最佳遗传模式;在超显性遗传模式中,把基因型A/A+G/G作为参考,基因型A/G在低级别宫颈鳞状上皮内病变组和高级别宫颈鳞状上皮内病变组中的比较P=:2×104, OR=2.83, 95%CI=1.61～4.99,差异有统计学意义,P0.05, AG基因型增加了低级别宫颈鳞状上皮内病变进一步发展为高级别宫颈鳞状上皮内病变的风险。[结论]1.hTERT基因 SNP 位点 rs2736122 (GA) , rs2853676 (C T),rs2075786(AG)多态性与宫颈癌前病变发生发展危险性无明显相关性。.2.hTERT基因SNP位点rs2853677 (AG)多态性与宫颈癌前病变发病风险性无明显相关性,但与宫颈癌前病变的发展存在相关性,A/G基因型可能增加了低级别宫颈鳞状上皮内病变进一步发展为高级别宫颈鳞状上皮内病变的风险。3.hTERT基因rs2075786/rs2736122单倍型分布与宫颈癌前病变的发生发展无明显相关性。
[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.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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