长寿人群HBB基因多态性对HBB mRNA血清表达水平的影响及其与代谢指标的关系

Effects of HBB polymorphisms on serum HBB mRNA expression and their associations with metabolic index in long-lived population

目的:探讨广西红水河流域长寿人群中HBB基因多态性对血清HBB mRNA表达水平的影响及其与代谢指标的关系。方法:采用实时荧光定量聚合酶链式反应(qRT-PCR)法对广西红水河流域长寿组168例及对照组196例进行血清HBB mRNA表达水平的检测,并使用PCR-Sanger测序法对HBB基因全长进行多态性检测,分析各多态性对HBB mRNA水平的影响及其与代谢指标的关系。结果:长寿组的血清HBB mRNA表达水平低于对照组(P<0.05);HBB基因检测出6个多态,其中长寿组rs7480526 A/A基因型的频率高于对照组(P<0.05);长寿组rs33986703基因型T/T及等位基因T的频率低于对照组(均P<0.05);长寿组rs7480526 A/A及rs33986703 T/T基因型的mRNA表达水平低于对照组(P<0.05,P<0.01);在总体人群中,rs7480526 A/A基因型携带者的TG水平低于A/C携带者(P<0.05),rs33986703 T/T携带者的ApoA1水平高于T/A携带者(P<0.05),这两个位点其他基因型携带者的代谢指标在长寿组及对照组之间无显著差异(P>0.05)。结论:HBB rs7480526及rs33986703基因多态可能通过表观遗传学影响HBB mRNA的表达,并参与对代谢指标的调控,进而影响衰老相关性疾病的发生发展及个体寿限。

Objectives:To explore the possible impacts of HBB gene polymorphisms on the serum expression of HBB mRNA and the association between polymorphisms and metabolic index in a longevous population living in Guangxi Hongshuihe River Basin.Methods:RT-qPCR technique was employed to measure the serum expression of HBB mRNA for long-lived group(n=168)and control group(n=196),and PCR-Sanger method was used to sequence the whole length of HBB gene to detect its polymorphism.The impacts of HBB polymorphisms on its serum expression and the associations between HBB genotypes and metabolic index were evaluated.Results:Serum expression of HBB mRNA in long-lived group was found to be higher than that of the control group(P<0.05);six polymorphisms were detected in HBB gene,in which the frequency of rs7480526 A/A genotype was significantly higher while rs33986703 T/T genotype was remarkably lower in long-lived group as compared with control group(all P<0.05);the expression of HBB mRNA of rs7480526 A/A and rs33986703 T/T carriers in long-lived group was significantly decreased in long-lived as compared to control group(P<0.05);in the combined population,the serum TG level of rs7480526 A/A carriers was markedly lower than A/C carriers while ApoA1 level of rs33986703 T/T carriers was higher than that of T/A carriers;other metabolic risk parameters of other genotypes had no differences among the three groups(P>0.05).Conclusion:HBB rs7480526 and rs33986703 polymorphisms may epigenetically involve in the regulation of HBB mRNA expression and metabolic parameters,which may impact the development of age-related disorders and thus individual lifespan.