云南不明原因猝死高发地区彝族人群心脏疾病相关基因变异

Cardiac Disease Associated Genetic Variants in Yi Nationality in Regions with High Incidence of Yunnan Sudden Unexplained Death

目的探究心脏疾病相关基因变异与云南不明原因猝死(Yunnan sudden unexplained death,YNSUD)在彝族人群高发的相关性。方法采集205例YNSUD高发地区彝族村民(病区组)和197例邻村健康彝族村民(对照组)的外周静脉血,提取基因组DNA,使用基质辅助激光解吸/电离-飞行时间质谱技术对25个心脏疾病相关基因的52个单核苷酸变异(single nucleotide variant,SNV)位点进行基因分型。采用SPSS 17.0软件分析数据,通过蛋白功能预测软件PolyPhen-2和SIFT对两组间差异具有统计学意义的位点进行致病性预测。使用十二导联心电图机对病区组所有个体进行心电图检测。结果致心律失常型右心室心肌病致病基因的错义变异位点DSG2(rs2278792,c.2318G>A,p.R773K)在病区组的等位基因频率及基因型频率均高于对照组(P<0.05)。病区组中有71例(34.6%)检出心电图异常,其中54例携带R773K变异。主要检见的心电图改变包括顺(逆)钟向转位、心电轴左(右)偏、ST段和T波改变以及传导阻滞等。结论对YNSUD高发地区彝族人群检测的52个心脏疾病相关基因的SNV位点,尚未发现明确的可致病性突变,彝族人群YNSUD高发的原因有待进一步研究。

Objective To explore the association of cardiac disease associated genetic variants and the high incidence of Yunnan sudden unexplained death(YNSUD)in Yi nationality.Methods The genomic DNA was extracted from peripheral blood samples collected from 205 Yi villagers from YNSUD aggregative villages(inpatient group)and 197 healthy Yi villagers from neighboring villages(control group).Fifty-two single nucleotide variants(SNVs)of 25 cardiac disease associated genes were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The SPSS 17.0 was used to analyze data.The pathogenicities of variants with differences between the two groups that have statistical significance were predicted by protein function prediction software Poly-Phen-2 and SIFT.All villagers from inpatient group were given electrocardiogram(ECG)examination using a 12-lead electrocardiograph.Results The allele frequency and the genotype frequency of missense mutation DSG2(rs2278792,c.2318G>A,p.R773K)of pathogenic genes of arrhythmogenic right ventricular cardiomyopathy(ARVC)in inpatient group was higher than that in control group(P<0.05).Abnormal ECG changes were detected in 71 individuals(34.6%)in the inpatient group,among which 54 individuals carried R773K mutation,including clockwise(counterclockwise)rotation,left(right)axis deviation,ST segment and T wave alteration and heart-blocking.Conclusion Definite pathogenic mutations have not been found in the 52 cardiac disease genes associated SNVs detected in Yi nationality in regions with high incidence of YNSUD.The cause of high incidence of YNSUD in Yi nationality needs further study.