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Asthma Gene (asthma + gene)

Distribution by Scientific Domains
Medical Sciences75%

Selected Abstracts

Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness

ALLERGY, Issue 6 2009
N. E. Reijmerink
Introduction:,ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV1) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. Aim:, To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene,environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. Methods:, Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV1 and BHR at age 8 years; asthma was based on questionnaire data at age 8. Results:, In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV1% predicted. Conclusions:, We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation. [source]

ORMDL3 , guilt by association?

CLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2008
M. Wjst
Summary A recent British,German study described ORMDL3 as a new asthma gene. Although the association with chromosome 17q12 marker is plausible from earlier linkage data, it is far from being clear which gene caused the association signal, as it is derived from a large linkage disequilibrium (LD) block. Not only Aiolos and GSDML but also distant genes that are regulated by this site may be relevant. There may be even unidentified RNA transcripts requiring a much more detailed genetic and functional analysis before finding ORMDL3 guilty by association. [source]

The importance of environment on respiratory genotype/phenotype relationships in the Inuit

ALLERGY, Issue 2 2010
P. V. Candelaria
To cite this article: Candelaria PV, Backer V, Khoo S-K, Bizzintino JA, Hayden CM, Baynam G, Laing IA, Zhang G, Porsbjerg C, Goldblatt J, LeSouëf PN, The Greenlandic Study Population Group. The importance of environment on respiratory genotype/phenotype relationships in the Inuit. Allergy 2010; 65: 229,237. Abstract Background:, Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype,phenotype associations in two geographically separated populations with common ancestry. Methods:, To accomplish this, two unselected populations of Inuit were recruited, one living in Greenland (n = 618) and the other in Denmark (n = 739). Subjects were genotyped for CD14 C-159T, SCGB1A1 A38G, ADRB2 Arg16Gly and Gln27Glu. The resulting genetic data were analysed for relationships with asthma-related parameters including lung function, ever asthma, atopy, rhinitis and dermatitis. Results:, The results showed contrasting magnitude and direction of genetic associations between the two geographically separate Inuit populations. In Greenland, the ADRB2 16Arg allele was associated with male-specific lower lung function, but in Denmark the same allele was associated with male-specific higher lung function. This allele was also associated with higher incidence of ever asthma in Denmark but not in Greenland. The SCGB1A1 38A allele was associated with lower rhinitis prevalence in Greenland but not in Denmark. Conclusions:, These associations suggest that environment interacts with candidate asthma genes to modulate asthma pathogenesis in the Inuit. [source]

Quantitative-trait-locus Mapping in the Presence of Locus Heterogeneity

ANNALS OF HUMAN GENETICS, Issue 6 2006
K Wang
Summary Locus heterogeneity is a concern for quantitative trait locus mapping where phenotypes are likely to be influenced by more than one gene. We introduce a model which generalizes the locus heterogeneity model of Smith (1961) from dichotomous traits to quantitative traits and consider some test statistics for this model. The type I error rates and the power of these statistics are assessed through simulation studies. These statistics are applied to a linkage study of asthma genes. [source]