NUP155基因突变与不明原因夜间猝死综合征及心律失常的关联性

Correlations among SUNDS,Arrhythmia and Variants in NUP155

【目的】研究中国汉族人群不明原因夜间猝死综合征(SUNDS)及心律失常病例中是否存在NUP155基因突变,并分析SUNDS及心律失常与NUP155基因突变的相关性。【方法】收集40例SUNDS案例和30例临床心律失常患者的外周血样本分别作为SUNDS组和临床组,以千人基因组数据库(1000 Genomes)与ExAC数据库中东亚人群作为人群对照组。应用基因芯片测序和Sanger测序对收集到的70例样本进行NUP155基因变异检测,通过Pearson卡方检验或Fisher′s精确检验(α=0.05)分析NUP155基因突变与SUNDS及心律失常的相关性。【结果】共检测到4个非同义突变(NUP155 c.4051A>G,p.N1351D、NUP155 c.2995-3012delCCTGGTCCTCCAGT?GTTG,p.P999-L1004del、NUP155 c.485G>T,p.162R>L、NUP155 c.485G>A,p.162R>Q),其中NUP155 c.2995-3012delCCTGGTCCTCCAGTGTTG,p.P999-L1004del和NUP155 c.485G>T,p.R162L为新发现的突变。SUNDS样本与ExAC数据库东亚人群的NUP155 cDNA第4051位碱基的构成比具有统计学差异(P<0.05),心律失常样本与ExAC数据库东亚人群的NUP155 cDNA第485位碱基的构成比具有统计学差异(P<0.05)。同时发现1个同义突变(NUP155 c.516C>T)、1个位于内含子的突变以及6个内含子多态性位点。【结论】中国汉族人群SUNDS和心律失常病例中存在NUP155基因突变,NUP155基因突变与SUNDS和心律失常具有相关性。

【Objective】To investigate NUP155 gene variants in the cases of sudden unexplained nocturnal death syndrome(SUNDS)and arrhythmia in the Chinese Han population,and to analyze the correlations between SUNDS,arrhythmia and NUP155 gene variants.【Methods】The SUNDS group and clinical group comprised 40 sporadic cases of SUNDS and 30 clinical cases of arrhythmia,respectively.The East Asian population data in 1000 Genomes database and ExAC database were used as the population control group.DNA microarray sequencing and Sanger sequencing were used to screen variants in NUP155 of 70 cases,and the associations between SUNDS,arrhythmia and variants in NUP155 was analyzed by Pearson chi-square test or Fisher′s exact test(P<0.05).【Results】Four non-synonymous mutations(NUP155 c.4051A>G,p.N1351D,NUP155 c.2995-3012delCCTGGTCCTCCAGTGTTG,p.P999-L1004del,NUP155 c.485G>T,p.162R>L,NUP155 c.485G>A,p.162R>Q)were detected.NUP155 c.2995-3012delCCTGGTCCTC?CAGTGTTG,p.P999-L1004del and NUP155 c.485G>T,p.R162L were newly found.There was a statistically signifi?cant difference(P<0.05)in the composition ratio of the 4051st base of NUP155 cDNA between SUNDS samples and ExAC database of East Asian population,and a statistically significant difference(P<0.05)in the composition ratio of the 485th base of NUP155 cDNA between the arrhythmia sample and ExAC database of East Asian population.A synony?mous mutation(NUP155 c.516C>T),an intron-located mutation,and six intron polymorphism sites were also selected.【Conclusions】Variants in NUP155 do exist in cases of SUNDS and arrhythmia in Chinese Han population,and mutations of NUP155 are associated with SUNDS and arrhythmia.