干扰素治疗慢性乙型肝炎预后与降钙素基因相关肽及受体活性蛋白1基因多态性的关联研究

张丽; 周琳; 高霞; 郑旭然; 杨孟茹; 张宁; 杨港; 刘文宣

Abstract

张丽,周琳,高霞,郑旭然,杨孟茹,张宁,杨港,刘文宣.干扰素治疗慢性乙型肝炎预后与降钙素基因相关肽及受体活性蛋白1基因多态性的关联研究[J].Chinese journal of Epidemiology,2020,41(6):924-928

干扰素治疗慢性乙型肝炎预后与降钙素基因相关肽及受体活性蛋白1基因多态性的关联研究

Study on the correlation between prognosis of patients with chronic hepatitis B under interferon treatment and polymorphism of both calcitonin gene related peptide and receptor activity modifying protein 1

Received:July 22, 2019

DOI：10.3760/cma.j.cn112338-20190722-00540

KeyWord: 慢性乙型肝炎干扰素降钙素基因相关肽受体活性蛋白1 单核苷酸多态性

English Key Word: Chronic hepatitis B Interferon therapy Calcitonin gene related peptide Receptor activity modifying protein 1 Single nucleotide polymorphism

FundProject:国家自然科学基金（81601876）；河北省自然科学基金（H2019206528）；河北省科技计划（132777246）；河北省高等学校科学技术研究（BJ2019019，QN2015006）；大学生创新性实验计划（USIP2018015，USIP2018245）

Author Name	Affiliation	E-mail
Zhang Li	Grade 2015, Preventive Medicine, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
Zhou Lin	Grade 2015, Preventive Medicine, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
Gao Xia	Department of Epidemiology and Statistics, Hebei Medical University, Shijiazhuang 050017, China
Zheng Xuran	Grade 2015, Preventive Medicine, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
Yang Mengru	Grade 2015, Preventive Medicine, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
Zhang Ning	Grade 2015, Preventive Medicine, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
Yang Gang	Grade 2015, Preventive Medicine, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
Liu Wenxuan	Department of Epidemiology and Statistics, Hebei Medical University, Shijiazhuang 050017, China	liuwenxuan1983@126.com

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Abstract:

目的探讨降钙素基因相关肽（CGRP） rs155209和受体活性蛋白1（RAMP1）rs3754701两个基因位点突变是否与干扰素治疗慢性乙型肝炎（乙肝）预后有关。方法采用调查问卷的方法收集317例研究对象的一般资料，收集其抗凝血，提取DNA，用基质辅助激光解吸电离飞行时间质谱实验平台进行SNPs分型，使用单因素及多因素logistic回归方法分析CGRP及RAMP1基因多态性与干扰素治疗慢性乙肝预后的关系。结果携带RAMP1基因rs3754701T者更容易出现DNA应答和ALT应答（OR=2.277，95% CI：1.386～3.741，P=0.001；OR=1.694，95% CI：1.073～2.675，P=0.024），而携带CGRP基因rs155209C者更不易出现DNA应答和ALT应答（OR=0.150，95% CI：0.083～0.271，P<0.001；OR=0.583，95% CI：0.367～0.925，P=0.022）。结论在中国北方汉族人群中，CGRP基因的rs155209和RAMP1基因的rs3754701位点与干扰素治疗慢性乙肝预后有关，rs3754701T在干扰素治疗后的DNA应答和ALT应答中起保护作用，而rs155209C携带者不易出现DNA应答和ALT应答。

English Abstract:

Objective To analyze the association of two single-nucleotide polymorphisms (SNP) ［Calcitonin gene related peptide (CGRP) rs155209 and receptor activity modifying protein 1 (RAMP1) rs3754701］ and the prognosis of chronic hepatitis B patients who were under interferon therapy. Methods A total of 317 patients and their anticoagulant blood samples were collected in this study. The SNPs in the CGRP and region RAMP1 were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Logistic regression method was used to assess the results from different phenotypic outcomes between cases and controls, after adjusted for sex and age in co-dominant, dominant and recessive genetic models. Results Data from this study clearly demonstrated the relevance of CGRP rs155209 and RAMP1 rs3754701 with DNA response and ALT response. RAMP1 rs3754701T was strongly associated with both DNA response and ALT response (OR=2.277, 95%CI: 1.386-3.741, P=0.001; OR=1.694, 95%CI: 1.073-2.675, P=0.024). However, CGRP rs155209C was less prone to DNA response and ALT response (OR=0.150, 95%CI: 0.083-0.271, P<0.001; OR=0.583, 95%CI: 0.367-0.925, P=0.022). Conclusions Results from our study suggested that both RAMP1 rs3754701 and CGRP rs155209 were associated with the prognosis of patients under interferon therapy in Han population, from the northern parts of China while RAMP1 rs3754701T was a protective factor for both ALT response and DNA response, but CGRP rs155209C carriers were less prone to DNA and ALT responses.

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