LPAR1 and ITGA4 Regulate Peripheral Blood Monocyte Counts

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, Jouke-Jan, Medland, Sarah E., Saviouk, Viatcheslav, Martin, Nicholas G., Visscher, Peter M., van Ommen, Gert-Jan B., Frazer, Ian H., Boomsma, Dorret I., Montgomery, Grant W. and Ferreira, Manuel A. R (2011) LPAR1 and ITGA4 Regulate Peripheral Blood Monocyte Counts. Human Mutation, 32 8: 873-876. doi:10.1002/humu.21536

Author 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, Jouke-Jan
Medland, Sarah E.
Saviouk, Viatcheslav
Martin, Nicholas G.
Visscher, Peter M.
van Ommen, Gert-Jan B.
Frazer, Ian H.
Boomsma, Dorret I.
Montgomery, Grant W.
Ferreira, Manuel A. R
Title LPAR1 and ITGA4 Regulate Peripheral Blood Monocyte Counts
Journal name Human Mutation   Check publisher's open access policy
ISSN 1059-7794
Publication date 2011-08
Sub-type Article (original research)
DOI 10.1002/humu.21536
Volume 32
Issue 8
Start page 873
End page 876
Total pages 4
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Collection year 2012
Language eng
Formatted abstract
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 (r2=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
Keyword Lysophosphatidic Acid
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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