PMID- 10051703
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20220330
IS  - 0954-7894 (Print)
IS  - 0954-7894 (Linking)
VI  - 29
IP  - 1
DP  - 1999 Jan
TI  - 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.
PG  - 60-71
AB  - 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-DRB1*11 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-DRB1*11 (25.6 vs 17.4%). In 
      contrast, the HLA-DRB1*1101+ 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-DRB1*1101, DQA1*0501, DQB1*0301 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-DRB1*1101, DQA1*0501, 
      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.
FAU - Lara-Marquez, M L
AU  - Lara-Marquez ML
AD  - Departamento de Alergia e Immunologia, Hospital Militar Carlos Arvelo, Sta Fe de 
      Bogota, Colombia.
FAU - Yunis, J J
AU  - Yunis JJ
FAU - Layrisse, Z
AU  - Layrisse Z
FAU - Ortega, F
AU  - Ortega F
FAU - Carvallo-Gil, E
AU  - Carvallo-Gil E
FAU - Montagnani, S
AU  - Montagnani S
FAU - Makhatadze, N J
AU  - Makhatadze NJ
FAU - Pocino, M
AU  - Pocino M
FAU - Granja, C
AU  - Granja C
FAU - Yunis, E
AU  - Yunis E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Antigens, Dermatophagoides)
RN  - 0 (Glycoproteins)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Antigens, Dermatophagoides
MH  - Asthma/blood/*genetics/*immunology
MH  - Child
MH  - Child, Preschool
MH  - Family Health
MH  - Female
MH  - Gene Frequency
MH  - Genes, MHC Class I
MH  - Genes, MHC Class II
MH  - Genetic Linkage
MH  - Glycoproteins/immunology
MH  - HLA-DQ Antigens/genetics
MH  - HLA-DQ alpha-Chains
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Haplotypes
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Lod Score
MH  - Male
MH  - Middle Aged
MH  - Skin Tests
MH  - Venezuela
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - 10.1046/j.1365-2222.1999.00461.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 1999 Jan;29(1):60-71. doi: 10.1046/j.1365-2222.1999.00461.x.