|
研究背景：英國研究人員日前報告發(fā)現(xiàn)了8個與衰老相關(guān)的基因，它們共同控制著人體內(nèi)一種名為DHEAS的類固醇的含量。人在20歲左右時，體內(nèi)DHEAS的含量達到最高峰，然后逐漸衰減，到85歲時可能只有峰值的5%。研究顯示，體內(nèi)DHEAS含量不足可能誘發(fā)多種疾病，如Ⅱ型糖尿病和淋巴瘤等。 英國倫敦國王學(xué)院研究人員在學(xué)術(shù)刊物《科學(xué)公共圖書館—遺傳學(xué)》（PLoS Genetics）上報告說，他們對歐洲和美國約1.5萬人進行了基因組分析，發(fā)現(xiàn)有8個基因控制著人體內(nèi)的DHEAS含量。 關(guān)鍵技術(shù)：GWAS 研究結(jié)果：進行14,846個人和確定了八個獨立的常見SNPs與血清中DHEAS濃度相關(guān)的全基因組關(guān)聯(lián)數(shù)據(jù)的薈萃分析, 達到或接近確定的位點的基因包括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）。 研究意義：這項研究提供了大量所需的數(shù)據(jù)，對于研究DHEAS的功能有重要意義。尋找調(diào)控這8個基因的方法，使人體內(nèi)DHEAS含量穩(wěn)定在較高水平，這或許能幫助人們更加健康長壽。 參考文獻：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. |
