维生素D受体基因多态性影响儿童流感临床结局的研究  

Association of single nucleotide polymorphisms in the vitamin D receptor gene with the clinical outcome of influenza in children

作　　者：张玉凤[1] 袁娟[1] 王军[1] 徐鹏飞[1] 刘瑞清[1] 唐甜甜 陈媛 邓慧玲[2] Zhang Yufeng;Yuan Juan;Wang Jun;Xu Pengfei;Liu Ruiqing;Tang Tiantian;Chen Yuan;Deng Huiling(Xi′an Children′s Hospital,Xi′an 710003,China;Xi′an Central Hospital,Xi′an 710003,China)

机构地区：[1]西安市儿童医院,710003 [2]西安市中心医院,710003

出　　处：《中国小儿急救医学》2022年第4期277-281,共5页Chinese Pediatric Emergency Medicine

基　　金：西安市卫生健康委员会科研项目(2020qn15);西安市中心医院院级项目(2021ZD05)。

摘　　要：目的探讨维生素D受体(VDR)基因单核苷酸多态性(SNP)与儿童流感易感性和病情严重程度的相关性。方法收集2019年2月至2021年2月西安市儿童医院及西安市中心医院收治的甲型流感患儿172例(研究组)和健康儿童88例(健康对照组)的外周静脉血,采用25-羟基维生素D(25-OH-D)试剂盒检测血清25-OH-D水平。根据临床表现将研究组分为轻症组、重症组和危重症组。选取VDR基因的4个候选位点ApaI、TaqI、FokI和BsmI,应用PCR-限制性片段长度多态性技术检测各组VDR基因的多态性并分析其与流感患儿临床结局之间的相关性。结果与健康对照组[(109.65±4.35)nmol/L]相比,研究组血清25-OH-D水平较低[轻症组(73.55±2.46)nmol/L,重症组(45.59±4.62)nmol/L,危重症组(33.65±3.87)nmol/L,P<0.05];研究组ApaI位点基因型AA、Aa及等位基因A(分别为51.74%、22.67%和63.08%)和FokI位点基因型FF、Ff及等位基因F(分别为41.86%、34.88%和59.30%)占比均显著高于健康对照组(依次分别为11.36%、14.77%、18.75%、10.23%、13.64%和17.05%)(P<0.05)。重症组ApaI位点等位基因A和基因型AA、Aa(分别为63.70%、43.84%和28.76%)的占比显著高于轻症组(分别为47.37%、35.09%和24.56%)(P<0.05);危重症组ApaI位点等位基因A和基因型AA、Aa(分别为92.86%、88.10%和49.52%)占比显著高于重症组(P<0.05)。血清25-OH-D<50 nmol/L(OR=5.087,95%CI 3.114-5.648)、ApaI位点基因型AA(OR=4.011,95%CI 1.217-18.624)和Aa(OR=3.839,95%CI 2.483-1.456)、FokI位点基因型FF(OR=4.112,95%CI 3.215-20.775)和Ff(OR=4.591,95%CI 0.032-10.936)是儿童流感发病的危险因素。结论血清25-OH-D缺乏与儿童流感的发生有关,VDR基因ApaI位点基因型AA、Aa和FokI位点基因型FF、Ff可增加儿童流感易感风险,ApaI位点等位基因A及基因型AA、Aa与流感的病情严重性有关。Objective To investigate the association of single nucleotide polymorphisms(SNPs)in the vitamin D receptor(VDR)gene with influenza susceptibility and severity of disease in children.Methods Peripheral venous blood was collected from 172 children with influenza A(study group)and 88 healthy children(healthy control group)admitted to Xi′an Children′s Hospital and Xi′an Central Hospital from February 2019 to February 2021.Serum 25-hydroxyvitamin D(25-OH-D)level was detected by using 25-OH-D kit.The study group was divided into three groups according to clinical syndrome:mild group,severe group,and critical group.Four candidate loci in the VDR gene(ApaI,TaqI,FokI,and BSMI)were selected,and polymorphisms in the VDR gene of each group were determined by polymerase chain reaction restriction fragment length polymorphism and analyzed in relation to children with influenza.Results Compared with the healthy control group[(109.65±4.35)nmol/L],the serum 25-OH-D levels in the study groups were lower[(73.55±2.46)nmol/L in the mild group,(45.59±4.62)nmol/L in the severe group,and(33.65±3.87)nmol/L in the critical group](P<0.05);Genotypes AA,Aa and allele A of the ApaI locus(51.74%,22.67%,and 63.08%,respectively)and genotypes FF,Ff and allele F of the FokI locus(41.86%,34.88%,and 59.30%,respectively)accounted for a significantly higher proportion of cases in the study group than those in healthy control group(11.36%,14.77%,18.75%,10.23%,13.64%,and 17.05%,respectively)(P<0.05).The proportion of allele A at the ApaI locus and genotypes AA and Aa in severe group(63.70%,43.84%,and 28.76%)were significantly higher than those in mild group(47.37%,35.09%,and 24.56%)(P<0.05);The proportion of allele A and genotype AA and at the ApaI locus in critical group(92.86%,88.10%,and 49.52%)were significantly higher than those in severe group(P<0.05).Serum 25-OH-D<50 nmol/L(OR=5.087,95%CI 3.114-5.648),ApaI site genotypes AA(OR=4.011,95%CI 1.217-18.624)and Aa(OR=3.839,95%CI 2.483-1.456),FokI site genotypes FF(OR=4.112,95%CI 3.215-20.775)a

关 键 词：维生素D受体 单核苷酸多态性 儿童 流感 

分 类 号：R725.1[医药卫生—儿科]