Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 26174136.
- Also identified by DOI 10.1038/ncomms8754 and PMC identifier 4518310.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Alpha-1 antitrypsin (AAT) encoded by SERPINA1 is an acute-phase inflammation marker, and AAT deficiency (AATD) is known as one of the common genetic disorders in European populations. However, no genetic determinants to AAT levels apart from the SERPINA gene clusters have been identified to date. Here we perform a genome-wide association study of serum AAT levels followed by a two-staged replication study recruiting a total of 9,359 Japanese community-dwelling population. Three missense variants of metabolic syndrome-related genes, namely, rs671 in ALDH2, rs1169288 in HNF1A and rs1260326 in GCKR, significantly associate with AAT levels (P≤1.5 × 10(-12)). Previous reports have shown the functional relevance of ALDH2 and HNF1A to AAT. We observe a significant interaction of rs671 and alcohol consumption on AAT levels. We confirm the association between AAT and rs2896268 in SERPINA1, which is independent of known causative variants of AATD. These findings would support various AAT functions including metabolic processes.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Aldehyde Dehydrogenase
- Hepatocyte Nuclear Factor 1-alpha
- Metabolic Syndrome
- alpha 1-Antitrypsin