Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23945879
TITLE
A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk.
ABSTRACT
The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ≈ 20 ng ml(-1) and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml(-1). Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16,705 asthmatics and 30,809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.
DATE PUBLISHED
2013 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/05/16
revised 2013/06/26
accepted 2013/07/03
aheadofprint 2013/08/15
entrez 2013/08/16 06:00
pubmed 2013/08/16 06:00
medline 2014/06/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Revez JA Revez J A JA Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Bain L Bain L L
Chapman B Chapman B B
Powell JE Powell J E JE
Jansen R Jansen R R
Duffy DL Duffy D L DL
Tung JY Tung J Y JY
AAGC Collaborators
Penninx BW Penninx B W BW
Visscher PM Visscher P M PM
De Geus EJ De Geus E J C EJ
Boomsma DI Boomsma D I DI
Hinds DA Hinds D A DA
Martin NG Martin N G NG
Montgomery GW Montgomery G W GW
Ferreira MA Ferreira M A R MA
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Matheson Melanie C MC
Marks B B
Hui Jennie J
Le Souëf Peter P
Danoy Patrick P
Baltic Svetlana S
Nyholt Dale R DR
Jenkins Mark M
Hayden Catherine C
Beilby John J
Cheah Faang F
Madden Pamela A PA
Heath Andrew C AC
Hopper John L JL
Musk Bill B
Leeder Stephen R SR
Walters Eugene H EH
James Alan A
Jones Graham G
Abramson Michael J MJ
Robertson Colin F CF
Dharmage Shyamali C SC
Brown Matthew A MA
Thompson Philip J PJ
JOURNAL
VOLUME: 14
ISSUE: 7
TITLE: Genes and immunity
ISOABBREVIATION: Genes Immun.
YEAR: 2013
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5470
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genes Immun
COUNTRY: England
ISSNLINKING: 1466-4879
NLMUNIQUEID: 100953417
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, American Recovery and Reinvestment Act
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
RC2 MH089951 NIMH NIH HHS United States
RC2 MH089951 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Asthma genetics
Case-Control Studies genetics
Child genetics
Female genetics
Genetic Predisposition to Disease genetics
Humans genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
RNA, Messenger metabolism
Receptors, Interleukin-6 metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 IL6R protein, human
0 RNA, Messenger
0 Receptors, Interleukin-6
OTHER ID's
OTHERID SOURCE
NIHMS635608 NLM
PMC4233139 NLM
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