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PTTG 1 IP and MAML 3 , novel genomewide association study genes for severity of hyperresponsiveness in adult asthma
Abstract Background The severity of bronchial hyperresponsiveness ( BHR ) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aimed to identify genes associ...
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Published in: | Allergy (Copenhagen) 2017-05, Vol.72 (5), p.792-801 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Abstract
Background
The severity of bronchial hyperresponsiveness (
BHR
) is a fundamental feature of asthma. The severity of
BHR
varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aimed to identify genes associated with
BHR
severity, using a genomewide association study (
GWAS
) on the slope of
BHR
in adult asthmatics.
Methods
We performed a
GWAS
on
BHR
severity in adult asthmatics from the Dutch Asthma
GWAS
cohort (
n
= 650), adjusting for smoking and inhaled corticosteroid use, and verified results in three other cohorts. Furthermore, we performed e
QTL
and co‐expression analyses in lung tissue.
Results
In the discovery cohort, one genomewide significant hit located in phosphodiesterase 4D, c
AMP
‐specif (
PDE
4D
) and 26
SNP
s with
P
‐values < 1*10
−5
were found. None of our findings replicated in adult and childhood replication cohorts jointly. In adult cohorts separately, rs1344110 in
pituitary tumour‐transforming 1 interacting protein
(
PTTG
1
IP
) and rs345983 in
Mastermind‐like 3
(
MAML
3
) replicated nominally; minor alleles of rs345983 and rs1344110 were associated with less severe
BHR
and higher lung tissue gene expression.
PTTG
1
IP
showed significant co‐expression with
pituitary tumour‐transforming 1
, the binding factor of
PTTG
1lP
, and with
vimentin
and
E‐cadherin1
.
MAML
3
co‐expressed significantly with
Mastermind‐like 2
(
MAML
2
), both involved in Notch signalling.
Conclusions
PTTG
1
IP
and
MAML
3
are associated with
BHR
severity in adult asthma. The relevance of these genes is supported by the e
QTL
analyses and co‐expression of
PTTG
1lP
with
vimentin
and
E‐cadherin1
, and
MAML
3
with
MAML
2
. |
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ISSN: | 0105-4538 1398-9995 |
DOI: | 10.1111/all.13062 |