CACNA1C基因的遗传多态性与慢性自发性荨麻疹易感性及预后的相关研究  

Association of CACNA1C gene genetic polymorphism with the susceptibility as well as prognosis for chronic spontaneous urticaria

作　　者：严晋洁 李清霖 罗宇雪 闫思聿 贺毅憬[1,3] 陈翔 YAN Jinjie1,2, LI Qinglin1,2, LUO Yuxue1,2, YAN Siyu1,3, HE Yijing1,3, CHEN Xiang1,3(1. Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008; 2. 2012 Grade Five Years of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha 410078; 3. Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, Chin)

机构地区：[1]中南大学湘雅医院皮肤科,长沙410008 [2]中南大学湘雅医学院2012级临床医学五年制,长沙410078 [3]皮肤肿瘤与银屑病湖南省重点实验室,长沙410008

出　　处：《中南大学学报（医学版）》2018年第9期929-936,共8页Journal of Central South University ：Medical Science

基　　金：国家级大学生创新与创业项目(201S1053336S).

摘　　要：目的:本实验选取CACNA1C基因3个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点rs58619945, rs7316246和rs216008,研究该基因多态性与慢性自发性荨麻疹发病以及非镇静类抗组胺药物疗效的相关性。方法:提取191名慢性自发性荨麻疹患者外周血全基因组DNA,并收集统计上述患者服用非镇静类抗组胺药物地氯雷他定、咪唑斯汀、非索非那定时荨麻疹疾病活动评分(Urticaria Activity Score 7,UAS7)及生活质量评分(Dermatology Life Quality Index,DLQI)的变化,通过PubMed检索系统选取可能与慢性荨麻疹发病相关的SNPs位点,即CACNA1C基因rs58619945,rs7316246和rs216008位点。将上述SNPs位点的等位基因型和等位基因数与千人基因组计划资料的对应数据进行对比,运用χ2检验完成基因型明确的189例患者和105例正常中国南方人群(千人基因组数据)不同基因型及等位基因频率之间易感性及使用非镇静类第二代抗组胺药疗效的比较。结果:慢性自发性荨麻疹患者携带CACNA1C rs58619945 G等位基因频率明显高于正常中国南方人群[OR(95%CI)=0.660(0.470~0.925),P=0.016],而rs7316246和rs216008位点的突变在两者之间的差异不具有统计学意义。并且以上3个SNPs位点与非镇静类第二代抗组胺药物治疗慢性自发性荨麻疹的总体疗效无明显相关性(rs58619945:OR=0.843,P=0.454;rs7316246:OR=2.103,P=0.102;rs216008:OR=0.237,P=0.363),但在单药分析时地氯雷他定的病例中rs216008位点的不同等位基因间疗效存在差异[OR(95%CI)=0.480(0.247~0.933),P=0.029],而咪唑斯汀的病例疗效未观察到与3个SNPs位点(rs58619945,rs7316246和rs216008)的相关性。结论:rs58619945位点在患者中的A/G突变可能与慢性自发性荨麻疹的发病相关,而rs216008位点的不同等位基因可能与地氯雷他定药物作用的疗效有关。Objective： To investigate the relationship between single nucleotide polymorphisms （SNPs） of CACNA1C （SNPs rs58619945, rs7316246 and rs216008） and susceptibility of chronic spontaneous urticaria （CSU） as well as the curative effect of non-sedating antihistamine drugs. Methods： Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 （UAS7） and Dermatology Life Quality Index （DLQI） changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs （rs58619945, rs7316246 and rs216008） of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs （desloratadine, mizolastine, fisofenadine） in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.Results： Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR（95%CI）=0.660（0.470–0.925）, P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls.Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs （rs58619945： OR=0.843, P=0.454; rs7316246： OR=2.103, P=0.102; rs216008： OR=0.237,P=0.363）. There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR（95%CI）=0.480（0.247–0.933）, P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine. Conclusion： The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.

关 键 词：慢性自发性荨麻疹 易感性 遗传多态性 CACNA1C基因 非镇静类第二代抗组胺药 

分 类 号：R758.24[医药卫生—皮肤病学与性病学]