|
|
| PMID |
|
|
| TITLE |
|
| LPAR1 and ITGA4 regulate peripheral blood monocyte counts. |
|
| 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 (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. |
| © 2011 Wiley-Liss, Inc. |
|
| DATE PUBLISHED |
|
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| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2011/04/12 |
| accepted |
2011/04/29 |
| entrez |
2011/05/21 06:00 |
| pubmed |
2011/05/21 06:00 |
| medline |
2011/12/14 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Maugeri N |
|
Maugeri |
Narelle |
N |
|
Queensland Institute of Medical Research, Brisbane, Australia. |
| Powell JE |
|
Powell |
Joseph E |
JE |
|
|
| 't Hoen PA |
|
't Hoen |
Peter A C |
PA |
|
|
| de Geus EJ |
|
de Geus |
Eco J C |
EJ |
|
|
| Willemsen G |
|
Willemsen |
Gonneke |
G |
|
|
| Kattenberg M |
|
Kattenberg |
Mathijs |
M |
|
|
| Henders AK |
|
Henders |
Anjali K |
AK |
|
|
| Wallace L |
|
Wallace |
Leanne |
L |
|
|
| Penninx B |
|
Penninx |
Brenda |
B |
|
|
| Hottenga JJ |
|
Hottenga |
Jouke-Jan |
JJ |
|
|
| Medland SE |
|
Medland |
Sarah E |
SE |
|
|
| Saviouk V |
|
Saviouk |
Viatcheslav |
V |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Visscher PM |
|
Visscher |
Peter M |
PM |
|
|
| van Ommen GJ |
|
van Ommen |
Gert-Jan B |
GJ |
|
|
| Frazer IH |
|
Frazer |
Ian H |
IH |
|
|
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Ferreira MA |
|
Ferreira |
Manuel A R |
MA |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 32 |
| ISSUE: 8 |
| TITLE: Human mutation |
| ISOABBREVIATION: Hum Mutat |
| YEAR: 2011 |
| MONTH: Aug |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1098-1004 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Hum Mutat |
| COUNTRY: United States |
| ISSNLINKING: 1059-7794 |
| NLMUNIQUEID: 9215429 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| R01D0042157-01A |
PHS HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Chromosome Mapping |
|
| Gene Expression Profiling |
|
| Gene Expression Regulation |
|
| Genotype |
|
| Humans |
|
| Integrin alpha4 |
metabolism |
| Leukocyte Count |
metabolism |
| Monocytes |
metabolism |
| Polymorphism, Single Nucleotide |
metabolism |
| Quantitative Trait Loci |
genetics |
| Receptors, Lysophosphatidic Acid |
metabolism |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Receptors, Lysophosphatidic Acid |
| 143198-26-9 |
Integrin alpha4 |
|
| OTHER ID's |
|
|
|
