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PLoS Genetics:发现8个与衰老相关基因
研究背景
        英国研究人员日前报告发现了8个与衰老相关的基因,它们共同控制着人体内一种名为DHEAS的类固醇的含量。人在20岁左右时,体内DHEAS的含量达到最高峰,然后逐渐衰减,到85岁时可能只有峰值的5%。研究显示,体内DHEAS含量不足可能诱发多种疾病,如Ⅱ型糖尿病和淋巴瘤等。
        英国伦敦国王学院研究人员在学术刊物《科学公共图书馆—遗传学》(PLoS Genetics)上报告说,他们对欧洲和美国约1.5万人进行了基因组分析,发现有8个基因控制着人体内的DHEAS含量。
关键技术
        GWAS
研究结果
        进行14,846个人和确定了八个独立的常见SNPs与血清中DHEAS浓度相关的全基因组关联数据的荟萃分析, 达到或接近确定的位点的基因包括ZKSCAN5(rs11761528; P = 3.15 × 10-36),SULT2A1(rs2637125,P = 2.61 × 10-19),ARPC1A(rs740160,P = 1.56 × 10-16),TRIM4(rs17277546 ,P = 4.50 × 10-11),BMF(rs7181230,P = 5.44 × 10-11),HHEX(rs2497306,P = 4.64 × 10-9),BCL2L11(rs6738028,P = 1.72 × 10-8),并CYP2C9(rs2185570,P = 2.29 × 10-8)。
研究意义
        这项研究提供了大量所需的数据,对于研究DHEAS的功能有重要意义。寻找调控这8个基因的方法,使人体内DHEAS含量稳定在较高水平,这或许能帮助人们更加健康长寿。
参考文献
        Zhai G, Teumer A, Stolk L, Perry JRB, Vandenput L, et al. (2011) Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms. PLoS Genet 7(4): e1002025. doi:10.1371/journal.pgen.1002025
Abstract :
        Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands—yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10−36), SULT2A1 (rs2637125; p = 2.61×10−19), ARPC1A (rs740160; p = 1.56×10−16), TRIM4 (rs17277546; p = 4.50×10−11), BMF (rs7181230; p = 5.44×10−11), HHEX (rs2497306; p = 4.64×10−9), BCL2L11 (rs6738028; p = 1.72×10−8), and CYP2C9 (rs2185570; p = 2.29×10−8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.




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