Contribution of ADAM33 polymorphisms to the population risk of asthma

J Blakey; E Halapi; U S Bjornsdottir; A Wheatley; S Kristinsson; R Upmanyu; K Stefansson; H Hakonarson; I P Hall

doi:10.1136/thx.2004.027227

Contribution of ADAM33 polymorphisms to the population risk of asthma

J Blakey
, E Halapi
, U S Bjornsdottir
, A Wheatley
, S Kristinsson
, R Upmanyu
, K Stefansson
, H Hakonarson
, I P Hall

Research output: Contribution to journal › Article › peer-review

91 Citations (Scopus)

Abstract

BACKGROUND: ADAM 33 is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results.

METHOD: To clarify the role of ADAM33 in determining the risk of asthma in the general population, new transmission disequilibrium and case-control studies were undertaken followed by a meta-analysis of all existing data.

RESULTS: Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta-analysis, however, showed that the F+1 and ST+7 variants were significantly associated with asthma in both types of study.

CONCLUSIONS: The additional risk imparted by this variation would account for 50,000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.

Original language	English
Pages (from-to)	274-6
Number of pages	3
Journal	Thorax
Volume	60
Issue number	4
DOIs	https://doi.org/10.1136/thx.2004.027227
Publication status	Published - Apr 2005
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1136/thx.2004.027227

Cite this

@article{1b09fbc2498747fb9cf40028ed6d28fd,

title = "Contribution of ADAM33 polymorphisms to the population risk of asthma",

abstract = "BACKGROUND: ADAM 33 is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results.METHOD: To clarify the role of ADAM33 in determining the risk of asthma in the general population, new transmission disequilibrium and case-control studies were undertaken followed by a meta-analysis of all existing data.RESULTS: Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta-analysis, however, showed that the F+1 and ST+7 variants were significantly associated with asthma in both types of study.CONCLUSIONS: The additional risk imparted by this variation would account for 50,000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.",

keywords = "ADAM Proteins, Asthma/genetics, Case-Control Studies, Chi-Square Distribution, Humans, Metalloendopeptidases/genetics, Polymorphism, Genetic/genetics, Risk Factors",

author = "J Blakey and E Halapi and Bjornsdottir, \{U S\} and A Wheatley and S Kristinsson and R Upmanyu and K Stefansson and H Hakonarson and Hall, \{I P\}",

year = "2005",

month = apr,

doi = "10.1136/thx.2004.027227",

language = "English",

volume = "60",

pages = "274--6",

journal = "Thorax",

issn = "0040-6376",

publisher = "BMJ Publishing Group",

number = "4",

}

TY - JOUR

T1 - Contribution of ADAM33 polymorphisms to the population risk of asthma

AU - Blakey, J

AU - Halapi, E

AU - Bjornsdottir, U S

AU - Wheatley, A

AU - Kristinsson, S

AU - Upmanyu, R

AU - Stefansson, K

AU - Hakonarson, H

AU - Hall, I P

PY - 2005/4

Y1 - 2005/4

N2 - BACKGROUND: ADAM 33 is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results.METHOD: To clarify the role of ADAM33 in determining the risk of asthma in the general population, new transmission disequilibrium and case-control studies were undertaken followed by a meta-analysis of all existing data.RESULTS: Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta-analysis, however, showed that the F+1 and ST+7 variants were significantly associated with asthma in both types of study.CONCLUSIONS: The additional risk imparted by this variation would account for 50,000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.

AB - BACKGROUND: ADAM 33 is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results.METHOD: To clarify the role of ADAM33 in determining the risk of asthma in the general population, new transmission disequilibrium and case-control studies were undertaken followed by a meta-analysis of all existing data.RESULTS: Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta-analysis, however, showed that the F+1 and ST+7 variants were significantly associated with asthma in both types of study.CONCLUSIONS: The additional risk imparted by this variation would account for 50,000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.

KW - ADAM Proteins

KW - Asthma/genetics

KW - Case-Control Studies

KW - Chi-Square Distribution

KW - Humans

KW - Metalloendopeptidases/genetics

KW - Polymorphism, Genetic/genetics

KW - Risk Factors

U2 - 10.1136/thx.2004.027227

DO - 10.1136/thx.2004.027227

M3 - Article

C2 - 15790980

SN - 0040-6376

VL - 60

SP - 274

EP - 276

JO - Thorax

JF - Thorax

IS - 4

ER -

Contribution of ADAM33 polymorphisms to the population risk of asthma

Abstract

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