A genome-wide search for quantitative trait loci underlying asthma

Daniels, S.E.; Bhattacharrya, Sudeepa; James, Alan; Leaves, N. I.; Young, Alexander I.; Hill, Mike; Faux, J. A.; Ryan, Gerard; Souëf, Peter N. Le; Lathrop, G.M.; Musk, Arthur W.; Cookson, William

doi:10.1038/383247a0

Cited by 723 publications

(516 citation statements)

References 27 publications

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“…This latter observation, although not significant on its own, is consistent with previously published evidence of excess sharing of maternal alleles at asthma susceptibility loci, [26][27][28] including markers flanking IL4RA. 29 There was no evidence that the potential disease association of À3223 C4T differed between the six populations (not shown).…”

Section: Resultssupporting

confidence: 91%

Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene

et al. 2003

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Variations in the interleukin 4 receptor A (IL4RA) gene have been reported to be associated with atopy, asthma, and allergy, which may occur less frequently in subjects with type 1 diabetes (T1D). Since atopy shows a humoral immune reactivity pattern, and T1D results from a cellular (T lymphocyte) response, we hypothesised that alleles predisposing to atopy could be protective for T1D and transmitted less often than the expected 50% from heterozygous parents to offspring with T1D. We genotyped seven exonic single nucleotide polymorphisms (SNPs) and the -3223 C4T SNP in the putative promoter region of IL4RA in up to 3475 T1D families, including 1244 Finnish T1D families. Only the À3223 C4T SNP showed evidence of negative association (P ¼ 0.014). There was some evidence for an interaction between À3233 C4T and the T1D locus IDDM2 in the insulin gene region (P ¼ 0.001 in the combined and P ¼ 0.02 in the Finnish data set). We, therefore, cannot rule out a genetic effect of IL4RA in T1D, but it is not a major one.

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Section: Resultssupporting

confidence: 91%

Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene

et al. 2003

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“…Indeed, linkage and molecular epidemiology studies have shown that several other such mediators (IL-4, IL-5, IL-13, interferon-␥) are candidates for susceptibility to asthma. [3][4][5] RANTES is produced by T-lymphocytes and monocytes and acts as a chemoattractant for several cell types (eg, mast cells, basophils, T-lymphocytes, eosinophils) 6,7 which are central to the inflammatory cascade. Therefore, increased production of RANTES would be predicted to result in enhanced recruitment of proinflammatory cells to the target site, precipitating an amplified local inflammatory reaction.…”

Section: Discussionmentioning

confidence: 99%

“…These include the interleukin-4 cytokine cluster on chromosome 5q31-33 (eg, IL-4, IL-5 and IL-13), and interferon-␥ on chromosome 12q. [3][4][5] A strong argument can be made for the chemokine RANTES as a candidate gene in asthma. This mediator has the ability to attract several types of inflammatory cells including monocytes, eosinophils and memory Thelper (Th) cells to the site of inflammation.…”

Section: Introductionmentioning

confidence: 99%

The −403 G→A promoter polymorphism in the RANTES gene is associated with atopy and asthma

et al. 2000

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Asthma is a complex inflammatory condition often associated with bronchial hyperreactivity and atopy. Genetic and environmental factors are implicated and several candidate genes have been implicated. Of these, the chemokine RANTES is responsible for the recruitment of inflammatory cells such as eosinophils and T-lymphocytes. We have recently identified a polymorphism within the RANTES promoter (−403 G →A) and have examined its role, using a PCR-RFLP assay, in the development of atopy and asthma in 201 Caucasian subjects. Atopic status was determined using skin prick testing and serum IgE levels. Severity of airway dysfunction was assessed using spirometric measurement (FEV 1 ) and methacholine challenge (PC 20 ). The −403 A allele was associated with an increased susceptibility to both atopy and asthma. Thus, the proportion of subjects carrying this allele was higher in each of atopic non-asthmatics, nonatopic asthmatics and atopic asthmatics compared with non-atopic, non-asthmatic controls. In particular, this allele was associated with skin test positivity but not IgE level. Homozygosity for the −403 A allele conferred a 6.5-fold increased risk of moderate/severe airway obstruction (FEV 1 р80% predicted), a marker for established asthma. Our data, whilst preliminary, indicate that the association of RANTES genotype with both atopy and asthma reflect independent effects, suggesting different mechanisms for the role of this chemokine in atopy and development of airway obstruction. Genes and Immunity (2000) 1, 509-514.

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“…Interestingly, potential susceptibility loci for several other autoimmune diseases have been mapped to the 16q region, as Crohn's disease [94], asthma [97], and IDDM [113].…”

Section: Linkage Studies Of Human Slementioning

confidence: 99%

The Genetics of Systemic Lupus Erythematosus

Lindqvist

Alarcón‐Riquelme

1999

Scand J Immunol

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Lindqvist AKB, Alarcón-Riquelme ME. The Genetics of Systemic Lupus Erythematosus. Scand J Immunol 1999;50:562-571. There is considerable evidence that the development of systemic lupus erythematosus (SLE) has a strong genetic basis. For more than 20 years, much effort has been made to understand the genetics of SLE. Association studies in humans suggest the existence of genetic effects by the alleles encoded in the HLA, deficiencies in the complement genes and the low-affinity variants of Fc␥-receptors. In mouse models of SLE at least 13 loci have been identified, including the MHC, linked to lupus-related phenotypes such as nephritis and production of autoantibodies. Recently, linkage studies have been performed in human SLE; one investigating a candidate region based on synteny to a murine susceptibility locus and four genome-wide linkage studies in various populations. Linkage was demonstrated to several chromosomal regions, some of which are syntenic to murine lupus susceptibility loci. Interestingly, many of the identified chromosomal regions co-localise with loci implicated in other autoimmune diseases.

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A genome-wide search for quantitative trait loci underlying asthma

Cited by 723 publications

References 27 publications

Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene

Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene

The −403 G→A promoter polymorphism in the RANTES gene is associated with atopy and asthma

The Genetics of Systemic Lupus Erythematosus

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