<i>KIR3DL1</i> rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化关系

沈超; 姚敏; 尹荣; 朱萍; 邵建国; 张津玮; 蔡卫华; 黄鹏; 董晨; 张云; 岳明

doi:10.11847/zgggws1135392

KIR3DL1 rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化关系

doi: 10.11847/zgggws1135392

沈超¹,
姚敏²,
尹荣³,
朱萍⁴,
邵建国⁵,
张津玮⁶,
蔡卫华⁷,
黄鹏^{1, 8},
董晨⁹,
张云^{1, 8, 10, ,},
岳明^11, ,

1.
南京医科大学公共卫生学院流行病与卫生统计学系传染病重点实验室, 江苏南京 211166
2.
南通大学医学院免疫学系
3.
南京医科大学附属江苏省肿瘤医院胸外科
4.
南京医科大学第一附属医院医务处
5.
南通大学附属南通市第三人民医院消化内科
6.
南京大学医学院附属鼓楼医院麻醉科
7.
南通大学附属南通市第三人民医院普外科
8.
南京医科大学全球健康中心
9.
苏州大学医学部公共卫生学院流行病与统计学系
10.
东部战区疾病预防控制中心传染病防控科
11.
南京医科大学第一附属医院感染病科

基金项目: 国家自然科学基金（81773499）；病毒学国家重点实验室开放研究基金（2019KF005）；江苏省优秀青年基金（BK20190106）；江苏省卫计委“科教强卫工程”青年医学人才项目（QNRC2016616）；云南省自然科学基金重点项目（2019FA005）；新发突发呼吸系统传染病临床研究中心（HS2020002）

详细信息

作者简介:
沈超（1995 – ），男，江苏常州人，硕士在读，研究方向：传染病流行病学

通讯作者:
张云，E-mail：zhangyunvip@126.com

岳明，E-mail：njym08@163.com

中图分类号: R 183
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- 文章访问数: 311
- HTML全文浏览量: 132
- PDF下载量: 24
- 被引次数: 0
出版历程
- 接收日期: 2021-05-10
- 网络出版日期: 2022-03-23
- 刊出日期: 2022-07-01

Association of SNP at KIR3DL1 rs35974949 and rs35656676 with HCV susceptibility and chronicity in high-risk populations

1.
Key Laboratory of Infectious Disease, Department of Epidemiology and Health Statistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China

摘要

摘要: 目的探讨KIR3DL1基因rs35974949和rs35656676位点单核苷酸多态性（SNP）与丙型肝炎病毒（HCV）易感性和慢性化的关联性，为定制HCV感染的筛查、诊断和个体化预防策略提供理论依据。方法于2008年8月 — 2015年12月采用整群抽样方法抽取江苏省句容市和丹阳市25个自然行政村1788名既往有偿献血者和江苏省9家三级医院肾透析中心749例肾透析者共2537名18～79岁未接受过抗HCV治疗（包括干扰素和直接抗病毒药物）的HCV感染高危人群进行问卷调查和HCV抗体检测，将抗 – HCV和HCV RNA均为阴性的1512人作为阴性组、抗 – HCV阳性且HCV RNA阴性的382人作为自限清除组、抗 – HCV和HCV RNA均为阳性的643人作为持续感染组，采用TaqMan探针实时荧光定量聚合酶链式反应（PCR）进行基因分型，并应用多因素logistic回归模型分析KIR3DL1基因rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化的关系。结果阴性组KIR3DL1 rs35974949位点GG、GT和TT型基因型携带者分别占78.47 %、20.05 % 和1.49 %，自限清除组分别占76.64 %、19.16 %和4.20 %，持续感染组分别占74.34 %、19.60 %和6.07 %；阴性组KIR3DL1 rs35656676位点CC、CG和GG型基因型携带者分别占31.32 %、50.60 %和18.08 %，自限清除组分别占31.68 %、49.74 %和18.59 %，持续感染组分别占31.78 %、50.47 %和17.76 %。在校正性别、年龄、谷丙转氨酶（ALT）值是否异常、谷草转氨酶（AST）值是否异常和感染途径后，多因素非条件logistic回归分析结果显示，与携带KIR3DL1 rs35974949位点GG/GT基因型的个体相比，携带KIR3DL1 rs35974949 位点TT基因型的个体更易感染HCV（共显性模型：OR = 2.802，95 % CI = 1.571～4.998，P < 0.001；隐性模型：OR = 2.860，95 % CI = 1.607～5.090，P < 0.001）；KIR3DL1 rs35974949位点基因多态性与HCV慢性化以及KIR3DL1基因rs35656676位点基因多态性与HCV易感性和慢性化均无相关性（均P > 0.05）。结论 KIR3DL1 rs35974949位点基因多态性与HCV易感性有关。
- 丙型肝炎病毒(HCV) /
- 易感性 /
- 慢性化 /
- 单核苷酸多态性(SNP) /
- 关系
Abstract: Objective To explore correlations of single nucleotide polymorphism (SNP) at KIR3DL1 rs35974949 and rs35656676 with the susceptibility and chronicity of hepatitis C virus (HCV) infection and to provide clinical evidences for screening, diagnosis and individualized prevention of HCV infection. Methods With cluster sampling from August 2008 to December 2015, we conducted face-to-face questionnaire interview, detections of HCV RNA, anti-HCV antibodies and other related serum indicators, and genotyping of KIR3DL1 r35974949 and rs35656676 with quantitative real-time PCR TaqMan assay among 2 537 people aged 18 – 79 years and at high risk of HCV infection but not ever having interferon and direct antiviral drug treatment, including 1 788 rural residents with paid blood donation history from 25 villages and 749 hemodialysis patients from 9 tertiary hospitals in Jiangsu province. According to detection results, the participants were then assigned into one of the three groups: uninfected control group (1 512 individuals) being seronegative for both anti-HCV antibodies and HCV RNA, spontaneous HCV clearance group (382) being seropositive for anti-HCV antibodies but seronegative for HCV RNA, and persistent HCV infection group (643) being seropositive for both anti-HCV antibodies and HCV RNA. Multivariate logistic regression models were used to analyze relationships between SNP at KIR3DL1 rs35974949 and rs35656676 and the susceptibility and chronicity of HCV infection. Results The proportions of KIR3DL1 rs35974949 GG, GT and TT genotype carriers were 78.47%, 20.05% and 1.49% in control group; 76.64%, 19.16% and 4.20% in spontaneous clearance group; and 74.34%, 19.60% and 6.07% in persistent HCV infection group; while, those of KIR3DL1 rs35656676 CC, CG and GG genotype carriers were 31.32%, 50.60% and 18.08% in control group; 31.68%, 49.74% and 18.59% in spontaneous clearance group; and 31.78%, 50.47% and 17.76% in persistent HCV infection group, respectively. After adjusting for gender, age, alanine aminotransferase (ALT) abnormality, aspartate aminotransferase (AST) abnormality and route of HCV infection, unconditional multivariate logistic regression analysis demonstrated that the individuals carrying KIR3DL1 rs35974949 TT genotype were more likely to have an increased HCV susceptibility (codominant model: adjusted odds ratio [aOR] = 2.802, 95% confidence interval [95% CI]: 1.571 – 4.998, P < 0.001; recessive genetic model: aOR = 2.860, 95% CI: 1.607 – 5.090, P < 0.001) compared with those carrying KIR3DL1 rs35974949 GG/GT genotype. However, no significant association of KIR3DL1 rs35974949 genotype with HCV chronicity was derived. Furthermore, no significant associations of KIR3DL1 rs35656676 polymorphism with HCV susceptibility and chronicity were observed. Conclusion Single nucleotide polymorphism at KIR3DL1 rs35974949 is associated with increased susceptibility of HCV infection in high risk populations.
- hepatitis C virus /
- susceptibility /
- chronicity /
- single nucleotide polymorphism /
- relationship

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表 1 KIR3DL1 rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化关系多因素非条件logistic回归分析

多态性位点	基因型	阴性组		自限清除组		持续感染组		自限清除组 + 持续感染组vs.阴性组			持续感染组vs.自限清除组
多态性位点	基因型	n	%	n	%	n	%	P 值	OR 值	95 % CI	P 值	OR 值	95 % CI
rs35974949	GG	1002	78.47	292	76.64	478	74.34		1.000			1.000
	GT	256	20.05	73	19.16	126	19.60	0.420	0.906	0.711～1.152	0.874	0.973	0.690～1.371
	TT	19	1.49	16	4.20	39	6.07	< 0.001	2.802	1.571～4.998	0.055	1.925	0.985～3.760
	显性模型							0.653	1.053	0.841～1.319	0.505	1.114	0.812～1.528
	相加模型							0.100	1.170	0.970～1.411	0.196	1.176	0.920～1.505
	隐性模型							< 0.001	2.860	1.607～5.090	0.052	1.936	0.994～3.767
rs35656676	CC	473	31.32	121	31.68	204	31.78		1.000			1.000
	CG	764	50.60	190	49.74	324	50.47	0.897	0.986	0.803～1.212	0.731	1.055	0.777～1.433
	GG	273	18.08	71	18.59	114	17.76	0.958	1.007	0.772～1.314	0.443	1.169	0.784～1.742
	显性模型							0.935	0.992	0.816～1.206	0.587	1.084	0.811～1.449
	相加模型							0.985	1.001	0.878～1.141	0.455	1.077	0.886～1.310
	隐性模型							0.896	1.016	0.804～1.283	0.493	1.131	0.796～1.606
注：a 调整了性别、年龄、ALT 值是否异常、AST 值是否异常和感染途径等混杂因素。

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