<i>MAPK1</i>与<i>NRAS</i>基因多态性与云南汉族人群宫颈上皮内瘤变的相关性

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

牛志鑫¹,
汤丽华²,
史磊¹,
洪超¹,
姚宇峰¹,
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

基金项目: 国家自然科学基金资助项目（82103190）；云南省基础研究计划基金资助项目（202201AY070001-139，202201AU070163）

详细信息

作者简介:
牛志鑫（1994～），女，河北张家口人，在读硕士研究生，主要从事肿瘤的免疫遗传学研究工作

通讯作者:
严志凌，E-mail：yanzhiling2021@126.com

中图分类号: R711.74
计量
- 文章访问数: 292
- HTML全文浏览量: 126
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2024-01-16
- 网络出版日期: 2024-04-29

Correlation of MAPK1 and NRAS Gene Polymorphisms with Cervical Intraepithelial Neoplasia in Yunnan Han Population

1.
Institute of Medical Biology，Chinese Academy of Medical Sciences & Peking Union Medical College，Kunming Yunnan 650118
2.
Dept. of Gynecology，The 1st People’s Hospital of Yuanmou County，Yuanmou Yunnan 651300
3.
Dept. of Gynecology，The 3rd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650118，China

摘要

摘要: 目的探讨在云南汉族人群中NRAS基因与MAPK1基因rs14804和rs9340多态性位点与宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）易感性的相关性。方法随机选取2017年5月至2019年10月昆明医科大学第三附属医院416例CIN患者和983例健康对照个体，通过TaqMan探针法对NRAS基因与MAPK1基因的SNPs位点（rs14804和rs9340）进行基因分型，分析2个SNPs位点与云南汉族人群CIN发生风险的相关性。结果 MAPK1基因的SNP位点rs9340等位基因（P = 0.008）和基因型（P = 0.002）在CIN组与对照组的分布频率差异具有统计学意义，等位基因A可能与更高的CIN发生风险相关（OR = 1.28，95%CI 1.07 ～ 1.54），尤其是低年龄组（≤ 50岁）人群的CIN风险相关（OR = 1.35，95%CI 1.09 ～ 1.67）。结论 MAPK1基因的SNP位点rs9340可能与云南汉族人群CIN发生风险具有相关性。
- 宫颈上皮内瘤变 /
- MAPK1 /
- NRAS /
- 单核苷酸多态性 /
- 相关性 /
- 云南汉族人群
Abstract: Objective NRAS and MAPK1 genes are important regulators of the Ras/Raf/MEK/ERK signaling pathway, and their functions and expression levels have been associated with a variety of human tumors. This study aims to investigate the correlation between the rs14804 and rs9340 polymorphic loci of NRAS and MAPK1 genes and the susceptibility to cervical intraepithelial neoplasia （CIN） in Yunnan Han population. Methods 1399 persons of the population were enrolled in the current study, with 416 as the CIN patient group and 983 as the healthy control group. The SNPs loci （rs14804 and rs9340） in the NRAS gene and the MAPK1 gene were genotyped using the TaqMan assays, and the correlation between the two SNPs loci and the risk of CIN was analyzed. Results The difference in the frequency of distribution of SNP locus rs9340 allele （P = 0.008） and genotype （P = 0.002） of MAPK1 gene in the CIN group versus the control group was statistically significant, and allele A may be associated with a higher risk of developing CIN （OR = 1.28, 95%CI 1.07 ～ 1.54）, especially for people in the lower age group （≤ 50 years） of CIN risk （OR = 1.35, 95%CI 1.09 ～ 1.67）. Conclusion rs9340 in the MAPK1 gene might be correlated with the risk of CIN in the Chinese Han population in Yunnan.
- Cervical intraepithelial neoplasia /
- MAPK1 /
- NRAS /
- Single nucleotide polymorphism /
- Correlation /
- Yunnan Han population

HTML全文

图 1 rs9340位点导致所在区域互补结合的miRNA发生改变

Figure 1. The rs9340 causes the different miRNA binding pattern

下载: 全尺寸图片幻灯片

表 1 选取病例的临床特征[（$ \bar{x} \pm s $），岁]

Table 1. The clinical characteristics of the subjects enrolled in this study [（$ \bar{x} \pm s $），years old]

分组	临床分期/年龄分层	n	年龄分布	t	P
对照组	高龄组	314	56.21 ± 3.85
	低龄组	718	41.91 ± 6.86
	总计	961	45.77 ± 8.87
CIN组	CIN2	51	45.59 ± 10.13	−1.535	0.903
	CIN3	365	44.92 ± 9.48	−2.923	0.137
	高龄组	102	58.09 ± 6.09	−3.523	4.8×10^−4*
	低龄组	265	40.75 ± 5.92	−2.771	0.006^*
	总计	416	45.00 ± 9.55	−1.446	0.148
^*P < 0.05。

下载: 导出CSV

表 2 2个SNPs位点在CIN和对照组间等位基因和基因型分布比较[n（%）]

Table 2. The comparison of allelic and genotypic distribution of the two SNPs between CIN and control groups[n（%）]

SNPs	等位基因/基因型	对照组	CIN组	χ²	P	OR（95%CI）
rs14804	A	49（2.50）	22（2.64）	0.055	0.815	1.06（0.64 ～ 1.77）
	G	1917（97.50）	810（97.36）	0.055	0.815	1.06（0.64 ～ 1.77）
	A/A	0（0.00）	1（0.24）	2.382	0.304
	A/G	49（4.98）	20（4.81）
	G/G	934（95.02）	395（94.95）
	HWE，P	0.423	0.177
rs9340	A	456（23.19）	232（27.88）	6.936	0.008^*	1.28（1.07 ～ 1.54）
	G	1510（76.81）	600（72.12）	6.936	0.008^*	1.28（1.07 ～ 1.54）
	A/A	55（5.60）	22（5.29）	12.568	0.002^*
	A/G	346（35.20）	188（45.19）
	G/G	582（59.20）	206（49.52）
	HWE，P	0.705	0.012
^*P < 0.025（统计学结果经Bonferroni校正，n = 2）。

下载: 导出CSV

表 3 高龄组和低龄组中rs9340位点与CIN的相关性分析[n（%）]

Table 3. The association of rs9340 with CIN in different age groups [n（%）]

年龄分层	等位基因/基因型	对照组	CIN组	χ²	P	OR（95%CI）
高年龄组	A	131（24.72）	55（26.96）	0.108	0.743	1.07（0.73 ～ 1.55）
	G	399（75.28）	149（73.04）	0.108	0.743	1.07（0.73 ～ 1.55）
	A/A	17（6.42）	4（3.92）	0.814	0.367	0.42（0.13 ～ 1.38）
	A/G	97（36.60）	47（46.08）	2.046	0.212	0.58（0.18 ～ 1.88）
	G/G	151（56.98）	51（50.00）	3.102	0.153
低年龄组	A	325（22.63）	177（28.18）	7.4	0.007^*	1.35（1.09 ～ 1.67）
	G	1111（77.37）	451（71.82）	7.4	0.007^*	1.35（1.09 ～ 1.67）
	A/A	38（5.29）	18（5.73）	10.37	0.001^*	1.59（1.19 ～ 2.08）
	A/G	249（34.69）	141（44.90）	0.898	0.343	1.33（0.74 ～ 2.38）
	G/G	431（60.02）	155（49.37）	10.453	0.005
^*P < 0.05。

下载: 导出CSV

表 4 rs9340位点与CIN分期进展的相关性[n（%）]

Table 4. Correlation of rs9340 locus polymorphism with different CIN stages [n（%）]

等位基因此/基因型	CIN2组	CIN3组	χ²	P	OR（95%CI）
A	22（21.57）	210（28.77）	2.323	0.127	0.68（0.41 ～ 1.12）
G	80（78.43）	520（71.23）	2.323	0.127	0.68（0.41 ～ 1.12）
A/A	1（1.96）	21（5.75）	1.515	0.218	0.28（0.04 ～ 2.14）
A/G	20（39.22）	168（46.03）	1.381	0.24	0.70（0.38～ 1.27）
G/G	30（58.82）	176（48.22）	0^b
^b该项为参照项，因此设置为0；^*P < 0.05。

下载: 导出CSV

表 5 rs9340位点对MAPK1基因3'UTR区域miRNA互补结合的影响

Table 5. The effect of rs9340 on miRNA binding to the 3'UTR of MAPK1

miRNA（miR）	靶基因新增/失去	位点起始位置	位点终止位置	在宫颈癌中发挥的作用
hsa-miR-153-3p	新增	21761059	21761065	circ_0005576/miR-153-3p/KIF20A通路驱动宫颈癌的增殖、迁移和侵袭^[25]
hsa-miR-448	新增	21761059	21761066	参与miRNA介导的转录后基因沉默
hsa-miR-210-3p	失去	21761057	21761064	宫颈癌组织中的miRNA-210-3p水平高于正常宫颈组织和CIN组织^[26]

下载: 导出CSV

参考文献(47)

[1]	Bruni L A G,Serrano B,Mena M,et al. Human papillomavirus and related diseases in the world [R]. Barcelona,Spain,2023: ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre),Summary Report 22 October 2021.
[2]	冯明月,闫萍. 宫颈上皮内瘤变诊治现状[J]. 河北医科大学学报,2020,41(4):480-483.
[3]	Schiffman M, Castle P E, Jeronimo J, et al. Human papillomavirus and cervical cancer[J]. Lancet (London, England),2007,370(9590):890-907.
[4]	Chen D,Cui T,Ek W E,et al. Analysis of the genetic architecture of susceptibility to cervical cancer indicates that common SNPs explain a large proportion of the heritability[J]. Carcinogenesis,2015,36(9):992-998. doi: 10.1093/carcin/bgv083
[5]	Vink J M,Van Kemenade F J,Meijer C J,et al. Cervix smear abnormalities: Linking pathology data in female twins,their mothers and sisters [J]. European Journal of Human Genetics : EJHG,2011,19(1): 108-111.
[6]	Zhang X,Zhang L,Tian C,et al. Genetic variants and risk of cervical cancer: Epidemiological evidence,meta-analysis and research review[J]. BJOG,2014,121(6):664-674. doi: 10.1111/1471-0528.12638
[7]	Hatzivassiliou G,Song K,Yen I,et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth[J]. Nature,2010,464(7287):431-435. doi: 10.1038/nature08833
[8]	Yuan J,Dong X,Yap J,et al. The MAPK and AMPK signalings: Interplay and implication in targeted cancer therapy[J]. Journal of Hematology & Oncology,2020,13(1):113.
[9]	Xie G,Zhu A,Gu X. Mitogen-activated protein kinase inhibition-induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma[J]. Head & Neck,2021,43(6):1721-1729.
[10]	Zhou G,Yang J,Song P. Correlation of ERK/MAPK signaling pathway with proliferation and apoptosis of colon cancer cells[J]. Oncology Letters,2019,17(2):2266-2270.
[11]	Bartholomeusz C,Gonzalez-Angulo A M,Liu P,et al. High ERK protein expression levels correlate with shorter survival in triple-negative breast cancer patients[J]. The Oncologist,2012,17(6):766-774. doi: 10.1634/theoncologist.2011-0377
[12]	Rauen K A. Defining RASopathy[J]. Dis Model Mech,2022,15(2):dmm049344. doi: 10.1242/dmm.049344
[13]	Yan Y,Gao Z,Han H,et al. NRAS expression is associated with prognosis and tumor immune microenvironment in lung adenocarcinoma[J]. J Cancer Res Clin Oncol,2022,148(3):565-575. doi: 10.1007/s00432-021-03842-w
[14]	Wang Y,Guo Z,Tian Y,et al. MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor[J]. BMC Cancer,2023,23(1):959. doi: 10.1186/s12885-023-11480-3
[15]	Harada G,Yang S R,Cocco E,et al. Rare molecular subtypes of lung cancer[J]. Nature Reviews Clinical Oncology,2023,20(4):229-249. doi: 10.1038/s41571-023-00733-6
[16]	Cicenas J,Tamosaitis L,Kvederaviciute K,et al. KRAS,NRAS and BRAF mutations in colorectal cancer and melanoma[J]. Medical Oncology (Northwood,London,England),2017,34(2):26. doi: 10.1007/s12032-016-0879-9
[17]	Ekedahl H, Cirenajwis H, Harbst K, et al. The clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort[J]. Br J Dermatol,2013,169(5):1049-1055.
[18]	Emrick M A,Hoofnagle A N,Miller A S,et al. Constitutive activation of extracellular signal-regulated kinase 2 by synergistic point mutations[J]. The Journal of Biological Chemistry,2001,276(49):46469-46479. doi: 10.1074/jbc.M107708200
[19]	Ojesina A I,Lichtenstein L,Freeman S S,et al. Landscape of genomic alterations in cervical carcinomas[J]. Nature,2014,506(7488):371-375. doi: 10.1038/nature12881
[20]	Insodaite R,Smalinskiene A,Liutkevicius V,et al. Associations of polymorphisms localized in the 3'UTR regions of the KRAS,NRAS,MAPK1 genes with laryngeal squamous cell carcinoma[J]. Genes,2021,12(11):1679. doi: 10.3390/genes12111679
[21]	国家癌症中心,国家肿瘤质控中心宫颈癌质控专家委员会. 中国宫颈癌规范诊疗质量控制指标(2022版)[J]. 中华肿瘤杂志,2022,44(7):615-622.
[22]	中华人民共和国国家卫生和计划生育委员会. 宫颈癌及癌前病变规范化诊疗指南(试行)[J]. 中国医学前沿杂志(电子版),2013,5(8):40-49.
[23]	Bhatla N,Aoki D,Sharma D N,et al. Cancer of the cervix uteri[J]. International Journal of Gynecology & amp; Obstetrics,2018,143(S2):22-36.
[24]	中华医学会妇产科学分会绝经学组. 中国绝经管理与绝经激素治疗指南2023版[J]. 中华妇产科杂志,2023,58(1):4-21.
[25]	Ma H,Tian T,Liu X,et al. Upregulated circ_0005576 facilitates cervical cancer progression via the miR-153/KIF20A axis[J]. Biomed Pharmacother,2019(10):109311. doi: 10.1016/j.biopha.2019.109311
[26]	Shao M X,Qu A Z,Wang Y Q,et al. Expression level of miRNA-210-3p in cervical cancer and its prognostic potential[J]. Eur Rev Med Pharmacol Sci,2020,24(12):6583-6588.
[27]	Bos J L. The ras gene family and human carcinogenesis[J]. Mutation Research,1988,195(3):255-271. doi: 10.1016/0165-1110(88)90004-8
[28]	Guin S,Theodorescu D. The RAS-RAL axis in cancer: Evidence for mutation-specific selectivity in non-small cell lung cancer[J]. Acta Pharmacologica Sinica,2015,36(3):291-297. doi: 10.1038/aps.2014.129
[29]	Lanfredini S,Thapa A,O'neill E. RAS in pancreatic cancer[J]. Biochemical Society Transactions,2019,47(4):961-972. doi: 10.1042/BST20170521
[30]	Afrăsânie V A,Marinca M V,Alexa-Stratulat T,et al. KRAS,NRAS,BRAF,HER2 and microsatellite instability in metastatic colorectal cancer - practical implications for the clinician[J]. Radiology and Oncology,2019,53(3):265-274. doi: 10.2478/raon-2019-0033
[31]	Li S,Balmain A,Counter C M. A model for RAS mutation patterns in cancers: Finding the sweet spot[J]. Nature Reviews Cancer,2018,18(12):767-777. doi: 10.1038/s41568-018-0076-6
[32]	Jakob J A,Bassett R L J r,Ng C S,et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma[J]. Cancer,2012,118(16):4014-4023. doi: 10.1002/cncr.26724
[33]	Schirripa M,Cremolini C,Loupakis F,et al. Role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer[J]. International Journal of Cancer,2015,136(1):83-90. doi: 10.1002/ijc.28955
[34]	Murphy B M, Terrell E M, Chirasani V R, et al. Enhanced BRAF engagement by NRAS mutants capable of promoting melanoma initiation[J]. Nat Commun,2022,13(1):3153.
[35]	Fu W,Zhuo Z,Hua R X,et al. Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk: A four-center case-control study[J]. Aging,2019,11(5):1551-1563. doi: 10.18632/aging.101855
[36]	Alessandro L,Low K E,Abushelaibi A,et al. Identification of NRAS diagnostic biomarkers and drug targets for endometrial cancer-an integrated in silico approach[J]. International Journal of Molecular Sciences,2022,23(22):14285. doi: 10.3390/ijms232214285
[37]	Jin M,Li Z,Sun Y,et al. Association analysis between the interaction of RAS family genes mutations and papillary thyroid carcinoma in the Han Chinese population[J]. International Journal of Medical Sciences,2021,18(2):441-447. doi: 10.7150/ijms.50026
[38]	Li S,Ma Y M,Zheng P S,et al. GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2 [J]. Journal of Experimental & Clinical Cancer Research : CR,2018,37(1): 80.
[39]	Yan Z,Ohuchida K,Fei S,et al. Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis [J]. Journal of Experimental & Clinical Cancer Research : CR,2019,38(1): 221.
[40]	Deng R,Zhang H L,Huang J H,et al. MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis[J]. Autophagy,2021,17(10):3011-3029. doi: 10.1080/15548627.2020.1850609
[41]	Wills C, Watts K, Maughan TS, et al. Germline variation in RASAL2 may predict survival in patients with RAS-activated colorectal cancer[J]. Genes Chromosomes Cancer,2023,62(6):332-341.
[42]	Campbell J D,Alexandrov A,Kim J,et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas[J]. Nature Genetics,2016,48(6):607-616. doi: 10.1038/ng.3564
[43]	Santos M,Lima L,Carvalho S,et al. The impact of BDNF,NTRK2,NGFR,CREB1,GSK3B,AKT,MAPK1,MTOR,PTEN,ARC,and SYN1 genetic polymorphisms in antidepressant treatment response phenotypes[J]. International Journal of Molecular Sciences,2023,24(7):6758. doi: 10.3390/ijms24076758
[44]	Zhu Y, Yang T, Duan J, et al. MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway[J]. Aging,2019,11(4):1089-109.
[45]	Guney G,Taşkın M I,Sener N,et al. The role of ERK-1 and ERK-2 gene polymorphisms in PCOS pathogenesis [J]. Reproductive Biology and Endocrinology : RB&E,2022,20(1): 95.
[46]	Wei H,Ke H L,Lin J,et al. MicroRNA target site polymorphisms in the VHL-HIF1α pathway predict renal cell carcinoma risk[J]. Molecular Carcinogenesis,2014,53(1):1-7. doi: 10.1002/mc.21917
[47]	Guo N,Zhang N,Yan L,et al. Correlation between genetic polymorphisms within the MAPK1/HIF-1/HO-1 signaling pathway and risk or prognosis of perimenopausal coronary artery disease[J]. Clinical Cardiology,2017,40(8):597-604. doi: 10.1002/clc.22708

相关文章(20)

[1]	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
[2]	洪超, 向旭东, 李盈甫, 曹杨, 陈雪雅, 李帅, 邢安灏, 林牧, 马千里. ERK1/2信号通路基因3'UTR多态性与非小细胞肺癌的相关性, 昆明医科大学学报. 2024, 45(3): 7-17. doi: 10.12259/j.issn.2095-610X.S20240302
[3]	陆小华, 袁洪新. BTLA、CTLA-4基因多态性与肝癌TACE联合靶向治疗疗效及预后相关性, 昆明医科大学学报. 2023, 44(9): 126-135. doi: 10.12259/j.issn.2095-610X.S20230927
[4]	程甜甜, 尹文卅, 王佳, 卢玉梅, 陈炫羽, 聂胜洁, 刘林林. TMTC1基因多态性与精神分裂症的关联性, 昆明医科大学学报. 2023, 44(10): 161-167. doi: 10.12259/j.issn.2095-610X.S20231014
[5]	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
[6]	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
[7]	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
[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]	马燕粉, 胡健, 蔡德佩, 乔永峰, 王晓琴. 3137例体检人群血清GGT水平和血脂指标的相关性研究, 昆明医科大学学报. 2022, 43(10): 115-121. doi: 10.12259/j.issn.2095-610X.S20221001
[10]	王娟娟, 陈雨青, 邓茜, 高健. 心肌酶谱与儿童1型糖尿病酮症酸中毒严重程度的相关性, 昆明医科大学学报. 2021, 42(1): 147-151. doi: 10.12259/j.issn.2095-610X.S20210129
[11]	阮小荟, 向茜, 王玉明, 周治含, 张弦, 郭燕, 杨晓瑞. 维生素D受体基因Bg1I、Cdx-2位点多态性与桥本氏甲状腺炎的相关性, 昆明医科大学学报. 2021, 42(8): 132-139. doi: 10.12259/j.issn.2095-610X.S20210824
[12]	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
[13]	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
[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]	赵金友. 云南省城市空巢老人孤独状况与生命质量相关性分析, 昆明医科大学学报. 2014, 35(07): -.
[20]	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): -.