Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A.
Author(s)
Type
Journal Article
Abstract
Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20 × 10-111) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22 × 10-11) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins. © 2010 Marzi et al.
Date Issued
2010-11-18
Online Publication Date
2010-11-18
2016-01-14T13:20:25Z
Date Acceptance
2010-10-20
ISSN
1553-7390
Publisher
Public Library of Science
Journal / Book Title
PLOS Genetics
Volume
6
Issue
11
Copyright Statement
© 2010 Marzi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Database
pubmed
Subjects
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 11
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Meta-Analysis as Topic
Serum Amyloid A Protein
Developmental Biology
0604 Genetics
Publication Status
Published
Article Number
e1001213