Premium
LPAR1 and ITGA4 regulate peripheral blood monocyte counts
Author(s) -
Maugeri Narelle,
Powell Joseph E.,
't Hoen Peter A.C.,
de Geus Eco J.C.,
Willemsen Gonneke,
Kattenberg Mathijs,
Henders Anjali K.,
Wallace Leanne,
Penninx Brenda,
Hottenga JoukeJan,
Medland Sarah E.,
Saviouk Viatcheslav,
Martin Nicholas G.,
Visscher Peter M.,
van Ommen GertJan B.,
Frazer Ian H.,
Boomsma Dorret I.,
Montgomery Grant W.,
Ferreira Manuel A.R.
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21536
Subject(s) - biology , monocyte , quantitative trait locus , downregulation and upregulation , gene , linkage disequilibrium , expression quantitative trait loci , gene expression , locus (genetics) , immunology , microbiology and biotechnology , genetics , allele , genotype , haplotype , single nucleotide polymorphism
We recently mapped a quantitative trait locus for monocyte counts to chromosome 9q31 (rs7023923). Here we extend this work by showing with two independent approaches that rs7023923 regulates the expression levels of the nearby LPAR1 gene ( P <0.0001), specifically implicating this gene in monocyte development. Furthermore, we tested 10 additional loci identified in the original analysis for replication in 1,122 individuals and confirm that rs6740847 near the alpha‐4‐integrin gene ( ITGA4 ) associates with variation in monocyte counts (combined P =2.7×10 −10 ). This variant is in complete linkage disequilibrium ( r 2 =1) with a previously reported eQTL for ITGA4 (rs2124440), indicating that this is the likely causal gene in the region. Our results indicate that rs7023923 and rs6740847 respectively upregulate LPAR1 and downregulate ITGA4 expression and this increases the number of monocytes circulating in the peripheral blood. Further studies that investigate the downstream mechanism involved and the impact on immune function are warranted. Hum Mutat 32:1–4, 2011. © 2011 Wiley‐Liss, Inc.