Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

Guangju Zhai, Alexander Teumer, Lisette Stolk, John R B Perry, Liesbeth Vandenput, Andrea D Coviello, Annemarie Koster, Jordana T Bell, Shalender Bhasin, Joel Eriksson, Anna Eriksson, Florian Ernst, Luigi Ferrucci, Timothy M Frayling, Daniel Glass, Elin Grundberg, Robin Haring, Asa K Hedman, Albert Hofman, Douglas P Kiel, Heyo K Kroemer, Yongmei Liu, Kathryn L Lunetta, Marcello Maggio, Mattias Lorentzon, Massimo Mangino, David Melzer, Iva Miljkovic, Alexandra Nica, Brenda W J H Penninx, Ramachandran S Vasan, Fernando Rivadeneira, Kerrin S Small, Nicole Soranzo, André G Uitterlinden, Henry Völzke, Scott G Wilson, Li Xi, Wei Vivian Zhuang, Tamara B Harris, Joanne M Murabito, Claes Ohlsson, Anna Murray, Frank H de Jong, Tim D Spector, Henri Wallaschofski

Journal: PLoS genetics 2011;7(4):e1002025

PMID: 21533175

Free Full Text on Public Library of Science View on PubMed

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.

Address: Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.

DOI: 10.1371/journal.pgen.1002025

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/olderadulthealth.html

MeSH Terms: Actin-Related Protein 2-3 Complex, Adaptor Proteins, Signal Transducing, Adult, Aged, Aging, Apoptosis Regulatory Proteins, Aryl Hydrocarbon Hydroxylases, Bcl-2-Like Protein 11, Cytochrome P-450 CYP2C9, DNA-Binding Proteins, Dehydroepiandrosterone Sulfate, Female, Gene Expression, Genome-Wide Association Study, Homeodomain Proteins, Humans, Kruppel-Like Transcription Factors, Linkage Disequilibrium, Liver, Male, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Sulfotransferases, Transcription Factors, White People, Young Adult