广西人群ULK1基因多态性与抗中性粒细胞胞浆抗体相关性血管炎的相关性  

Correlation of polymorphisms in ULK1 gene with ANCA-associated vasculitis in Guangxi population

作　　者：饶金兰 朱艳 何佩耕 黎伟[2] 黄莉[2] 薛超[2] RAO Jinlan;ZHU Yan;HE Peigeng;LI Wei;HUANG Li;XUE Chao(The Second Clinical Medical College of Guangxi Medical University,Nanning 530021,China;不详)

机构地区：[1]广西医科大学第二临床医学院,南宁530021 [2]广西医科大学第二附属医院肾内科,南宁530007

出　　处：《实用医学杂志》2020年第19期2661-2666,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金地区科学基金项目(编号:81360117);广西自然科学基金(编号:2018GXNSFAA281122);广西医疗卫生适宜技术开发与推广应用项目(编号:S2017010)。

摘　　要：目的探究ULK1基因的rs9652059、rs7953348和rs748808位点与广西人群抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic autoantibody,ANCA)相关性血管炎(ANCA-associated vasculitis,AAV)的相关性。方法采用多重PCR结合高通量测序技术对入选的177例原发性AAV患者(AAV组)和210例健康体检者(对照组)各位点进行基因分型,比较等位基因频率及基因型分布,进行遗传模型、连锁不平衡和单体型分析。结果ULK1的rs9652059等位基因C和rs7953348等位基因T为AAV的风险等位基因(P=0.028,OR=1.412,95%CI:1.038~1.919)。在显性模型(P=0.022,OR=1.66,95%CI:1.07~2.56)和对数加性模型(P=0.043,OR=1.40,95%CI:1.01~1.94)下,rs9652059和rs7953348与AAV的发生存在强关联性。在隐性模型下,携带TT+TC(rs9652059)、CC+CT(rs7953348)的AAV患者具有相对更高的中性粒细胞、红细胞计数、血红蛋白含量及C反应蛋白水平,差异有统计学意义(均P<0.05)。rs748808在两组间的等位基因频率及基因型分布的差异均无统计学意义(P>0.05)。rs9652059和rs7953348完全连锁不平衡。以TCT为参照,单体型CTT增加了AAV的发病风险(OR=1.42,95%CI:1.02~1.98,P=0.039)。结论ULK1基因rs9652059、rs7953348位点的多态性可能与广西人群AAV的易感性相关,且与中性粒细胞、红细胞计数、血红蛋白含量及C反应蛋白水平相关。Objective The aim of this study tired to investigate the relationships amongst SNPs rs9652059,rs7953348 and rs748808 of ULK1 and AAV in Guangxi population.Methods The aforementioned SNPs of ULK1 were genotyped by multiplex polymerase chain reaction(PCR)combined with high-throughput sequencing of cases(n=177)and controls(n=210).Moreover,Allele frequency and genotype distribution were compared and linkage unbalance and haplotype of genetic model were also analyzed.Results The rs9652059 allele C.and rs7953348 allele T increased the risk of AAV in the allele model(both as P=0.028,OR=1.412,95%CI:1.038-1.919).In the genetic model analysis,the rs9652059 and rs7953348 increased the risk of AAV in the dominant model(both as P=0.022,OR=1.66,95%CI:1.07~2.56),and the log-additive model(both as P=0.043,OR=1.40,95%CI:1.01~1.94).AAV patients with TT+TC(rs9652059)and CC+CT(rs7953348)had a relatively higher count of neutrophil,RBC,hemoglobin and CRP levels in the recessive model(Both as P<0.05).Positive correlation between rs748808 and AAV was not observed(P>0.05).SNPs rs9652059 and rs7953348 were completely linkage disequilibrium.Compared with TCT,haplotype CTT increased the risk of AAV(OR=1.42,95%CI:1.02~1.98,P=0.039).Conclusions The SNPs rs9652059 and rs7953348 ofULKl related to the occurrence of AAV in Guangxi population.Also,they were associated with neutrophil,RBC count,hemoglobin content and CRP level in AAV.

关 键 词：ULK1 抗中性粒细胞胞浆抗体相关性血管炎 自噬 多态性 单核苷酸 

分 类 号：R543[医药卫生—心血管疾病]