RGD Reference Report - Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.

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Immunogenetics of atopic asthma: association of DRB11101 DQA10501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.
Authors:	Lara-Marquez, ML Yunis, JJ Layrisse, Z Ortega, F Carvallo-Gil, E Montagnani, S Makhatadze, NJ Pocino, M Granja, C Yunis, E
Citation:	Lara-Marquez ML, etal., Clin Exp Allergy 1999 Jan;29(1):60-71.
RGD ID:	1331670
Pubmed:	PMID:10051703 (View Abstract at PubMed)
BACKGROUND: Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. OBJECTIVE: To study the influence of the MHC class I and class II genes in the susceptibility to atopic asthma. METHODS: MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). RESULTS: MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.0 17, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB111 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC = 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB111 (25.6 vs 17.4%). In contrast, the HLA-DRB11101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC<0.05). The HLA-DRB11101, DQA10501, DQB10301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC< 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P<0.001) and Der f (median, 46.9 vs 2.7 kU/L, P<0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. CONCLUSIONS: We have identified an association between the haplotype HLA-DRB11101, DQA10501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
H2-Aa	Mouse	asthma		ISO	HLA-DQA1 (Homo sapiens)	DNA:polymorphism (human)	RGD
H2-Eb1	Mouse	asthma		ISO	HLA-DRB1 (Homo sapiens)	DNA:polymorphism (human)	RGD
HLA-DQA1	Human	asthma		IAGP		DNA:polymorphism (human)	RGD
HLA-DRB1	Human	asthma		IAGP		DNA:polymorphism (human)	RGD
RT1-Ba	Rat	asthma		ISO	HLA-DQA1 (Homo sapiens)	DNA:polymorphism (human)	RGD
RT1-Db1	Rat	asthma		ISO	HLA-DRB1 (Homo sapiens)	DNA:polymorphism (human)	RGD

Objects Annotated

Genes (Rattus norvegicus)

RT1-Ba (RT1 class II, locus Ba)

RT1-Db1 (RT1 class II, locus Db1)

Genes (Mus musculus)

H2-Aa (histocompatibility 2, class II antigen A, alpha)

H2-Eb1 (histocompatibility 2, class II antigen E beta)

Genes (Homo sapiens)

HLA-DQA1 (major histocompatibility complex, class II, DQ alpha 1)

HLA-DRB1 (major histocompatibility complex, class II, DR beta 1)

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Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.

Immunogenetics of atopic asthma: association of DRB11101 DQA10501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.