BAG3基因单核苷酸多态性与中国北方汉族人群克山病的关联研究

An association between single nucleotide polymorphisms of Bcl-2 related anti apoptotic protein 3 gene and Keshan disease in north Chinese Han population

目的 探讨中国北方汉族人群Bcl-2相关抗凋亡蛋白3（BAG3）基因的多态性与克山病患者之间的关系。方法 血样来自于2002年在陕西省黄陵县以285例汉族人群研究对象，包括79例克山病患者（病例组）和206例健康对照人群（对照组），由西安交通大学地方病防治研究所提供，- 80 ℃保存。从外周血中提取基因组DNA，采用飞行时间质谱分型技术对候选位点进行基因分型。使用SPSS 16.0和TYPER 4.0软件包对数据进行统计学分析。应用拟合优度χ2检验分析基因频率分布是否符合哈迪-温伯格（Hardy-Weinberg）定律，应用χ^2检验对病例和对照组的基因型和等位基因进行关联分析。应用Logistic回归分析方法对年龄进行校正后再次对病例和对照组的基因型进行关联分析。结果 病例和对照组在BAG3基因上的rs2234962、rs196295、rs3858339和rs3858340位点基因频率分布均符合Hardy-Weinberg平衡（P均 〉 0.05）。病例组在4个位点（rs2234962：CC、CT、TT分别为0.0%、0.0%、100.0%，rs196295：GG、GA、AA分别为22.8%、54.4%、22.8%，rs3858339：GG、GT、TT分别为5.1%、38.0%、56.9%，rs3858340：TT、TC、CC分别为5.1%、38.0%、56.9%）与对照组基因型频率（rs2234962：CC、CT、TT分别为0.0%、1.0%、99.0%，rs196295：GG、GA、AA分别为21.4%、51.5%、26.2%，rs3858339：GG、GT、TT分别为5.8%、34.5%、59.7%，rs3858340：TT、TC、CC分别为5.8%、34.5%、59.7%）比较差异无统计学意义（χ^2 = 0.685、0.408、0.330、0.330，P均 〉 0.05）。经年龄校正后，BAG3基因上4个位点基因型频率分布差异无统计学意义（χ^2 = 0.001、0.019、1.009、0.019，P均 〉 0.05）。结论 BAG3基因上的rs2234962、rs196295、rs3858339和rs3858340位点基因多态性与中国北方地区汉族人群克山病无相关性。

Objective To investigate the relationship between single nucleotide polymorphisms of Bcl-2 related anti apoptotic protein 3 （BAG3） gene and Keshan disease （KD） in north Chinese Han population. Methods In 2002 a total of 285 Chinese Han subjects, including 79 KD patients and 206 control subjects were involved in this study. Genomic DNA was extracted from the peripheral venous blood sample. Blood samples were provided by the Institute of Endemic Disease Prevention, Xi’an Jiaotong University, and stored at 80 °C. The polymorphism of genetic variation was genotyped by matrix-assisted laser desorption/ionization-time of flight （MALDI-TOF）. The data was analyzed using TYPER 4.0 or SPSS16.0 software. All sample groups were tested for Hardy-Weinberg equilibrium using goodness-of-fit χ2 test. Differences in genotype distribution and allele frequencies between case and control were compared by χ2 test. Logistic regression analysis was applied to detect association using age as a confounding factor. Results All sample group passed the Hardy-Weinberg equilibrium test （P 〉 0.05）. Significant differences were not observed in genotype distribution between cases （rs2234962： CC, CT, TT were 0.0%, 0.0% and 100.0%, respectively; rs196295： GG, GA, AA were 22.8%, 54.4% and 22.8%, respectively; rs3858339： GG, GT, TT were 5.1%, 38.0% and 56.9%, respectively; rs3858340： TT, TC, CC were 5.1%, 38.0% and 56.9%, respectively） and controls （rs2234962： CC, CT, TT were 0.0%, 1.0% and 99.0%, respectively; rs196295： GG, GA, AA were 21.4%, 51.5% and 26.2%, respectively; rs3858339： GG, GT, TT were 5.8%, 34.5% and 59.7%, respectively; rs3858340： TT, TC, CC were 5.8%, 34.5% and 59.7%, respectively） for rs2234962, rs3858339, rs196295 and rs3858340 on BAG3 gene （χ2 = 0.685, 0.408, 0.330, 0.330，P 〉 0.05）. Significant differences were not observed in genotype after age-correcting between cases and controls for 4 SNPs on BAG3 gene （χ2 = 0.001, 0.019, 1.009, 0.019, P 〉 0.05）. Conclusion The results suggest that the BAG3 gene might not be a susceptibility gene of KD in north Chinese Han population.