miR-146a基因多态性与宫颈上皮内瘤变的相关性

师雨晗; 柴江红; 许金美; 林牧; 姚宇峰; 何凤权; 严志凌

miR-146a基因多态性与宫颈上皮内瘤变的相关性

师雨晗¹,
柴江红²,
许金美³,
林牧⁴,
姚宇峰¹,
何凤权^5, ,,
严志凌^{2, 3, ,}

1.
中国医学科学院 & 北京协和医学院医学生物学研究所，云南昆明　650118
2.
元谋县第一人民医院妇产科，云南元谋　651300
3.
昆明医科大学第三附属医院妇科，云南昆明　650118
4.
云南省保山市第二人民医院检验科，云南保山　678000
5.
红河州妇幼保健院妇产科，云南红河　661199

基金项目: 云南省基础研究计划基金（202201AY070001-139）；保山市科技计划项目-2023年医学研究联合专项基金（2023bskjylms016）

详细信息

作者简介:
师雨晗（2002～），女，云南昆明人，在读硕士研究生，主要从事肿瘤的免疫遗传学工作

通讯作者:
何凤权，E-mail：569451434@qq.com

严志凌，E-mail：yanzhiling2021@126.com

中图分类号: R737.33
计量
- 文章访问数: 10
- HTML全文浏览量: 7
- PDF下载量: 3
- 被引次数: 0
出版历程
- 收稿日期: 2024-09-12

The Association between miR-146a Gene Polymorphism and Cervical Intraepithelial Neoplasia

Yuhan SHI¹,
Jianghong CHAI²,
Jinmei XU³,
Mu LIN⁴,
Yufeng YAO¹,
Fengquan HE^{5
, ,},
Zhiling YAN^{2, 3
, ,}

1.
Institute of Medical Biology，Chinese Academy of Medical Sciences & Peking Union Medical College，Kunming Yunnan 650118
2.
Department of Obstetrics and Gynecology，The 1st People’s Hospital of Yuanmou County，Yuanmou Yunnan 651300
3.
Department of Gynaecologic Oncology，The 3rd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650118
4.
Department of Laboratory Medicine，Baoshan 2nd People’s Hospital，Baoshan Yunnan 678000
5.
Department of Obstetrics and Gynecology，Maternal and Child Health Hospital of Honghe Prefecture，Honghe Yunnan 661199，China

摘要

摘要: 目的探究miR-146a基因的单核苷酸多态性（single nucleotide polymorphisms，SNP）rs57095329、rs6864584与宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）的相关性。方法利用SPSS软件随机收集96例CIN患者作为CIN组，225名健康个体作为对照组，采用TaqMan探针法方法对以上SNP位点进行基因分型，分析其与CIN的相关性。结果 rs57095329位点的等位基因和基因型分布相对于对照组差异具有统计学意义，CIN组中等位基因A的频率显著低于对照组（P < 0.001；OR = 0.48，95%CI：0.32～0.70）；在显性模式下，携带G等位基因（A/G-G/G）的个体CIN发生风险显著升高（P < 0.001；OR = 2.67，95% CI：1.64～4.37）。但rs6864584位点与CIN的发生风险及组织学分期均无相关性。结论 miR-146a基因rs57095329位点的A等位基因可能是CIN的保护性因素。
- MicroRNAs /
- 宫颈上皮内瘤变 /
- 单核苷酸多态性 /
- 云南汉族人群
Abstract: Objective To investigate the association between single nucleotide polymorphisms （SNP） rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia （CIN） in Yunnan Han population. Method A total of 96 patients diagnosed with CIN in the Third Affiliated Hospital of Kunming Medical University were randomly collected as the CIN group, and 225 healthy individuals examined during the same period were selected as the control group using SPSS software. Genotyping of the above SNP loci was performed using the TaqMan probe method. and their correlation with CIN was analyzed. Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group. with the frequency of the allele A in the CIN group significantly lower than that in the control group （P < 0.001; OR = 0.48, 95%CI: 0.32～0.70）. In the dominant model, individuals carrying the G allele （A/G-G/G） had a significantly increased risk of CIN （P < 0.001; OR = 2.67, 95%CI: 1.64～4.37）. In contrast, no correlation was found between the rs6864584 and the risk of CIN or histological staging （P > 0.016）. Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.
- MicroRNAs /
- Cervical intraepithelial neoplasia /
- Single nucleotide polymorphisms /
- Han population in Yunnan

HTML全文

图 1 rs5709539参与的DNA特征和调控元件

Figure 1. DNA features and regulatory elements involved in rs5709539

下载: 全尺寸图片幻灯片

图 2 rs57095329对SPI1表达的eQTL分析

Figure 2. eQTL analysis of rs57095329 on SPI1 expression

下载: 全尺寸图片幻灯片

表 1 SNP位点的等位基因和基因型在对照组和CIN组中的分布特征[n （%）]

Table 1. Distribution characteristics of allele and genotype at SNP loci in the control group and CIN group [n （%）]

SNPs	等位基因/基因型	对照组	CIN组	HWE		对照组 vs CIN组
SNPs	等位基因/基因型	对照组	CIN组	χ²	P	χ²	P	OR （95%CI）
rs57095329	A	370（82.2）	132（68.8）	0.742	0.389	14.325	< 0.001^*	0.48[0.32～0.70]
	G	80（17.8）	60（31.2）
	A/A	154（68.4）	43（44.8）			15.888	< 0.001^*
	A/G	62（27.6）	46（47.9）
	G/G	9（4.0）	7（7.3）
rs6864584	C	38（8.4）	13（6.8）	0.116	0.733	0.515	0.473	0.79[0.41～1.51]
	T	412（91.6）	179（93.2）
	C/C	2（0.9）	0（0.0）			1.014	0.602
	C/T	34（15.1）	13（13.5）
	T/T	189（84.0）	83（86.5）
^*P < 0.025。

下载: 导出CSV

表 2 SNP位点在对照组和CC、CIN中的遗传模式分析[n （%）]

Table 2. Genetic model analysis of SNP loci in the control，CC，and CIN groups [n （%）]

SNPs	模型	基因型	对照组 n （%）	CIN组 n （%）	对照组 vs CIN组
SNPs	模型	基因型	对照组 n （%）	CIN组 n （%）	χ²	P	OR （95%CI）
rs57095329	共显性	A/A	154（68.4）	43 （44.8）	14.555	< 0.001	1.00
		A/G	62 （27.6）	46 （47.9）			2.66（1.60～4.42）
		G/G	9 （4.0）	7 （7.3）			2.79（0.98～7.91）
	显性	A/A	154（68.4）	43 （44.8）	15.879	< 0.001	1.00
		A/G-G/G	71 （31.6）	53 （55.2）			2.67（1.64～4.37）
	隐性	A/A-A/G	216（96.0）	89 （92.7）	1.539	0.230	1.00
		G/G	9 （4.0）	7 （7.3）			1.89（0.68～5.23）
	超显性	A/A-G/G	163（72.4）	50 （52.1）	12.496	< 0.001	1.00
		A/G	62 （27.6）	46 （47.9）			2.42（1.47～3.97）
	逻辑累加	---	---	---	17.055	< 0.001	2.12（1.42～3.16）
rs6864584	共显性	T/T	189（84.0）	83 （86.5）	0.155	0.450	1.00
		T/C	34 （15.1）	13 （13.5）			0.87（0.44～1.73）
		C/C	2 （0.9）	0 （0.0）			---
	显性	T/T	189（84.0）	83 （86.5）	0.314	0.570	1.00
		T/C-C/C	36 （16.0）	13 （13.5）			0.82（0.41～1.63）
	隐性	T/T-T/C	223（99.1）	96（100.0）	0.859	0.230	1.00
		C/C	2 （0.9）	0 （0.0）			---
	超显性	T/T-C/C	191（84.9）	83 （86.5）	0.133	0.710	1.00
		T/C	34 （15.1）	13 （13.5）			0.88（0.44～1.75）
	逻辑累加	---	---	---	0.519	0.470	0.79（0.41～1.51）

下载: 导出CSV

参考文献(41)

[1]	Jemal A,Bray F,Center M M,et al. Global cancer statistics[J]. CA Cancer J Clin,2011,61(2):69-90. doi: 10.3322/caac.20107
[2]	Chen W,Zheng R,Baade P D,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132. doi: 10.3322/caac.21338
[3]	De freitas A C,Gurgel A P,Chagas B S,et al. Susceptibility to cervical cancer: An overview[J]. Gynecol Oncol,2012,126(2):304-311. doi: 10.1016/j.ygyno.2012.03.047
[4]	Zur hausen H. Papillomaviruses in the causation of human cancers-A brief historical account[J]. Virology,2009,384(2):260-265. doi: 10.1016/j.virol.2008.11.046
[5]	Siegler E,Shiner M,Segev Y,et al. Prevalence and Genotype Distribution of HPV Types in Women at Risk for Cervical Neoplasia in Israel[J]. Isr Med Assoc J,2017,19(10):635-639.
[6]	Virolainen S J,Vonhandorf A,Viel K C M F,et al. Gene–environment interactions and their impact on human health[J]. Genes & Immunity,2023,24(1):1-11.
[7]	Crosbie E J,Einstein M H,Franceschi S,et al. Human papillomavirus and cervical cancer[J]. Lancet,2013,382(9895):889-899. doi: 10.1016/S0140-6736(13)60022-7
[8]	Fang J,Li Y,Zhang J,et al. Correlation between polymorphisms in microRNA-regulated genes and cervical cancer susceptibility in a Xinjiang Uygur population[J]. Oncotarget,2017,8(19):31758-31764. doi: 10.18632/oncotarget.15970
[9]	李娅亨,杨希,杨佳,等. miR-155和miR-200b基因多态性与云南汉族人群宫颈癌及宫颈上皮内瘤变的相关性[J]. 贵阳医学院学报,2021,046(5):504-510.
[10]	刘伟鹏,许金美,杨佳,等. miR-34a,miR-155及miR-486基因多态性与宫颈癌前病变和宫颈癌相关性研究[J]. 中华肿瘤防治杂志,2022,29(07):488-493.
[11]	Bartel D P. Metazoan MicroRNAs[J]. Cell,2018,173(1):20-51. doi: 10.1016/j.cell.2018.03.006
[12]	张云云. EGFL7和miR-126参与肺癌发生风险的遗传分析和功能研究 [D]. 北京协和医学院,2022.
[13]	Wang J Y,Chen L J. The role of miRNAs in the invasion and metastasis of cervical cancer[J]. Biosci Rep,2019,39(3):BSR20181377. doi: 10.1042/BSR20181377
[14]	Jia H,Cao M,Hao S,et al. Prediction of prognosis,immune infiltration and immunotherapy response with N6-methyladenosine-related lncRNA clustering patterns in cervical cancer[J]. Scientific Reports,2022,12(1):17256. doi: 10.1038/s41598-022-20162-2
[15]	Ma Q,Yu W,Li Z,et al. Circ_0081723 enhances cervical cancer progression and modulates CREBRF via sponging miR-545-3p[J]. Naunyn Schmiedebergs Arch Pharmacol,2024,397(11):8839-8852. doi: 10.1007/s00210-024-03175-8
[16]	Gao W,Hua J,Jia Z,et al. Expression of miR-146a-5p in breast cancer and its role in proliferation of breast cancer cells[J]. Oncol Lett,2018,15(6):9884-9888.
[17]	Sandhu R,Rein J,D'arcy M,et al. Overexpression of miR-146a in basal-like breast cancer cells confers enhanced tumorigenic potential in association with altered p53 status[J]. Carcinogenesis,2014,35(11):2567-2575. doi: 10.1093/carcin/bgu175
[18]	Yue C,Wang M,Ding B,et al. Polymorphism of the pre-miR-146a is associated with risk of cervical cancer in a Chinese population[J]. Gynecol Oncol,2011,122(1):33-37. doi: 10.1016/j.ygyno.2011.03.032
[19]	Pecorelli S. Revised FIGO staging for carcinoma of the vulva,cervix,and endometrium[J]. Int J Gynaecol Obstet,2009,105(2):103-104. doi: 10.1016/j.ijgo.2009.02.012
[20]	Schiffman M,Castle P E,Jeronimo J,et al. Human papillomavirus and cervical cancer[J]. Lancet,2007,370(9590):890-907. doi: 10.1016/S0140-6736(07)61416-0
[21]	郭妮,张承,洪超,等. KRAS基因3'UTR多态性与云南汉族人群宫颈癌及宫颈上皮内瘤变的相关性[J]. 昆明医科大学学报,2024,45(2):14-22. doi: 10.12259/j.issn.2095-610X.S20240203
[22]	牛志鑫,汤丽华,史磊,等. MAPK1与NRAS基因多态性与云南汉族人群宫颈上皮内瘤变的相关性[J]. 昆明医科大学学报,2024,45(5):8-15. doi: 10.12259/j.issn.2095-610X.S20240502
[23]	Shi Y Y,He L. SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J]. Cell Res,2005,15(2):97-98. doi: 10.1038/sj.cr.7290272
[24]	Hu Z,Zhu D,Wang W,et al. Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism[J]. Nat Genet,2015,47(2):158-163. doi: 10.1038/ng.3178
[25]	Zhou X,Chen X,Hu L,et al. Polymorphisms involved in the miR-218-LAMB3 pathway and susceptibility of cervical cancer,a case-control study in Chinese women[J]. Gynecol Oncol,2010,117(2):287-290. doi: 10.1016/j.ygyno.2010.01.020
[26]	Xie K,Chen M,Zhu M,et al. A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in Chinese population[J]. Int J Cancer,2017,141(5):958-966. doi: 10.1002/ijc.30788
[27]	Mir R,Al balawi I A,Duhier F M A. Involvement of microRNA-423 Gene Variability in Breast Cancer Progression in Saudi Arabia[J]. Asian Pac J Cancer Prev,2018,19(9):2581-2589.
[28]	Yan Z,Zhou Z,Li C,et al. Polymorphisms in miRNA genes play roles in the initiation and development of cervical cancer[J]. J Cancer,2019,10(20):4747-4753. doi: 10.7150/jca.33486
[29]	Wu Y,Hao X,Feng Z,et al. Genetic polymorphisms in miRNAs and susceptibility to colorectal cancer[J]. Cell Biochem Biophys,2015,71(1):271-278. doi: 10.1007/s12013-014-0195-y
[30]	Liu H,Zhou Y,Liu Q,et al. Association of miR-608 rs4919510 polymorphism and cancer risk: a meta-analysis based on 13,664 subjects[J]. Oncotarget,2017,8(23):37023-37031. doi: 10.18632/oncotarget.9509
[31]	Bastami M,Choupani J,Saadatian Z,et al. Evidences from a systematic review and meta-analysis unveil the role of miRNA polymorphisms in the predisposition to female neoplasms[J]. Int J Mol Sci,2019,20(20):5088. doi: 10.3390/ijms20205088
[32]	Srivastava S,Singh S,Fatima N,et al. Pre-microRNA gene polymorphisms and risk of cervical squamous cell carcinoma[J]. J Clin Diagn Res,2017,11(9):GC01-GC04.
[33]	Min P,Li W,Zeng D,et al. A single nucleotide variant in microRNA-1269a promotes the occurrence and process of hepatocellular carcinoma by targeting to oncogenes SPATS2L and LRP6[J]. Bull Cancer,2017,104(4):311-320. doi: 10.1016/j.bulcan.2016.11.021
[34]	Mortazavi-jahromi S S,Aslani M,Mirshafiey A. A comprehensive review on miR-146a molecular mechanisms in a wide spectrum of immune and non-immune inflammatory diseases[J]. Immunology Letters,2020,227(1):8-27.
[35]	Luo X,Yang W,Ye D Q,et al. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus[J]. PLoS Genet,2011,7(6):e1002128. doi: 10.1371/journal.pgen.1002128
[36]	Cammaerts S,Strazisar M,De rijk P,et al. Genetic variants in microRNA genes: impact on microRNA expression,function,and disease[J]. Front Genet,2015,6(1):186.
[37]	Hefzy E M,Hassuna N A,Shaker O G,et al. miR-155 T/A (rs767649) and miR-146a A/G (rs57095329) single nucleotide polymorphisms as risk factors for chronic hepatitis B virus infection among Egyptian patients[J]. PLoS One,2021,16(8):e0256724. doi: 10.1371/journal.pone.0256724
[38]	Yu M,Al-dallal S,Al-haj L,et al. Transcriptional regulation of the proto-oncogene Zfp521 by SPI1 (PU. 1) and HOXC13[J]. Genesis,2016,54(10):519-533. doi: 10.1002/dvg.22963
[39]	Tao L,Wang X,Zhou Q. Long noncoding RNA SNHG16 promotes the tumorigenicity of cervical cancer cells by recruiting transcriptional factor SPI1 to upregulate PARP9[J]. Cell Biol Int,2020,44(3):773-784. doi: 10.1002/cbin.11272
[40]	Zhang J,Tan H,Cao Q,et al. Meta-analysis of miRNA variants associated with susceptibility to autoimmune disease[J]. Dis Markers,2021,2021(1):9978460.
[41]	Salimi S,Sargazi S,Mollashahi B,et al. Association of polymorphisms in miR146a,an inflammation-associated microRNA,with the risk of idiopathic recurrent spontaneous miscarriage: a case-control study[J]. Dis Markers,2022,2022(1):1495082.

相关文章(20)

[1]	陈雪雅, 许金美, 李智, 梁燕, 姚宇峰, 何凤权, 严志凌. HOXD-AS2、MIR3142HG基因多态性与宫颈上皮内瘤变的相关性, 昆明医科大学学报. 2024, 45(11): 16-21. doi: 10.12259/j.issn.2095-610X.S20241103
[2]	郭妮, 张承, 洪超, 刘伟鹏, 姚宇峰, 严志凌. KRAS基因3′UTR多态性与云南汉族人群宫颈癌及宫颈上皮内瘤变的相关性, 昆明医科大学学报. 2024, 45(2): 14-22. doi: 10.12259/j.issn.2095-610X.S20240203
[3]	牛志鑫, 汤丽华, 史磊, 洪超, 姚宇峰, 严志凌. MAPK1与NRAS基因多态性与云南汉族人群宫颈上皮内瘤变的相关性, 昆明医科大学学报. 2024, 45(5): 8-15. doi: 10.12259/j.issn.2095-610X.S20240502
[4]	伍蓉霜, 彭江丽, 陈永刚, 陈洁, 马国伟, 李先蕊, 李谢, 余春红. SLC2A9基因单核苷酸多态性与吡嗪酰胺致高尿酸血症易感性关系, 昆明医科大学学报. 2023, 44(4): 40-47. doi: 10.12259/j.issn.2095-610X.S20230409
[5]	李吉, 柯坤彬, 张白羽, 刘裔道, 白晶, 董滔, 王振丞, 秦德强, 王梦悦, 李颢. 云南德宏州傣族人群CaSR基因SNP与含钙肾结石和高钙尿的关联性, 昆明医科大学学报. 2023, 44(5): 72-80. doi: 10.12259/j.issn.2095-610X.S20230520
[6]	李抒瑾, 杨艳飞, 苏敏, 凌昱, 饶艳琼, 崔继华. 儿童注意缺陷多动障碍共病情绪问题的单核苷酸多态性研究, 昆明医科大学学报. 2023, 44(4): 139-147. doi: 10.12259/j.issn.2095-610X.S20230420
[7]	师雨晗, 李菁, 刘舒媛, 赵婷, 杨净思, 史荔, 梁疆莉. 壮族人群ERAP基因多态性与脊灰疫苗序贯免疫诱导的抗体应答的相关性分析, 昆明医科大学学报. 2023, 44(7): 22-28. doi: 10.12259/j.issn.2095-610X.S20230711
[8]	梁燕, 王磊, 雷鸣, 陈本超, 孙萍, 李帅, 刘莉, 王倩蓉, 廖曼霖, 马千里. KRAS基因多态性与云南汉族人群非小细胞肺癌的相关性分析, 昆明医科大学学报. 2023, 44(2): 52-60. doi: 10.12259/j.issn.2095-610X.S20230210
[9]	谭丁及, 尹洪莉, 朱锐, 张曦, 余鑫, 飞勇, 李昕, 段铭, 何亮, 杨宏英. 宫颈上皮内瘤变和宫颈癌患者的阴道微生态特点, 昆明医科大学学报. 2021, 42(8): 118-122. doi: 10.12259/j.issn.2095-610X.S20210821
[10]	李东云, 冮顺奎, 李捷, 张明星, 李雷. ABCG2、SLC2A9、SLC17A3和 PRKG2基因单核苷酸位点多态性与哈尼族人群痛风的关系, 昆明医科大学学报. 2021, 42(3): 54-60. doi: 10.12259/j.issn.2095-610X.S20210320
[11]	杨佳, 李娅娴, 王莹莹, 肖琳, 李传印, 谭芳, 马千里, 刘舒媛. 云南汉族人群mircoRNA-149、mircoRNA-219、mircoRNA-let-7基因多态性与非小细胞肺癌发生和发展的相关性, 昆明医科大学学报. 2021, 42(10): 22-28. doi: 10.12259/j.issn.2095-610X.S20211037
[12]	朱胜章. 宫颈液基细胞学检查在贵州黔南地区宫颈癌筛查中的临床运用, 昆明医科大学学报. 2016, 37(08): -.
[13]	李轶梅. 宫颈环行电刀切除术治疗宫颈上皮内瘤变的临床价值, 昆明医科大学学报. 2016, 37(02): -.
[14]	向茜. 维生素D受体基因FokI位点单核苷酸多态性与糖尿病肾病的相关性, 昆明医科大学学报. 2016, 37(04): -.
[15]	刘城秀. 云南汉族人群TNF-α基因和ALCAM基因多态性与HCV慢性感染的相关性, 昆明医科大学学报. 2016, 37(05): -.
[16]	刘丽丽. 染色体9p21单核苷酸多态性与冠心病/心肌梗死相关性的研究进展, 昆明医科大学学报. 2015, 36(08): -1.
[17]	戴书颖. IL-4基因启动子SNP-1098T>G和-590C>T多态性与云南汉族人群HCV慢性感染的相关性研究, 昆明医科大学学报. 2015, 36(03): -1.
[18]	李莹. 云南汉族人群IL-10基因启动子多态性与HCV慢性感染的相关性研究, 昆明医科大学学报. 2015, 36(01): -1.
[19]	杨小蕾. STAT4基因单核苷酸多态性与云南汉族人群SLE发病的相关性研究, 昆明医科大学学报. 2013, 34(06): -.
[20]	黄雅. Brn-3a、PPAR-γ在宫颈癌及癌前病变中的表达, 昆明医科大学学报. 2008, 29(01): -.