THE ASSOCIATION BETWEEN HLA-DR, -DQ GENES AND SUSCEPTIBILITY TO ATOPY IN A BIRTH COHORT

Abstract

ISEE-202 Introduction: Atopic disease in early childhood plays a major role in the development of asthma in childhood or adolescence. Different human leukocyte antigen (HLA) class II alleles have been associated with the development of atopic asthma and responsiveness of allergen exposure. HLA class II molecules were found in neonates’ immune system. However, the relationship between the atopic disease in early childhood and HLA-DR and -DQ genes remains unclear. Aim: Our aim is to determine the association between HLA-DR and -DQ genes and susceptibility to atopy in a birth cohort at one year follow-up. Methods: Four private maternity hospitals were randomly selected to participate and recruit pairs of mothers and neonates. A questionnaire was administered to collect demographic data, home environment, family disease histories, and information about atopic symptoms including early-onset transient wheezing, atopic dermatitis, and eczema, diagnosed by paediatricians. The questionnaire was completed by neonates’ parents when neonates were followed up to the age of 1 year by telephone interview. The levels of cord blood IgE (cIgE) and maternal total IgE (sIgE) and allergen-specific IgE were determined by the Pharmacia UniCAP IgE assay test system. HLA-DR and -DQ alleles were typed using the Dynal AllSet+™ “low resolution” SSP kit. Results: Between July 2001 and May 2003, 187 mother and neonate pairs participated in this study. A total of 184 neonates completed the HLA-DR and -DQ genotyping. The frequencies of HLA-DR and -DQ genes, maternal sensitization, sIgE > 100 IU/ml, and cIgE ≥ 0.35 IU/ml were not different between the four areas. No association was found between cIgE and HLA-DR and -DQ genes or atopic symptoms. Physician diagnosed atopic symptoms were associated with the HLA-DQB1*02 allele (X2= 10.38, p<0.0013). After adjusting for possible potential risk factors, the sIgE > 100 IU/ml (Odds Ratio (OR) =5.01, 95% ci= [1.22, 27.14]), and HLA-DQB1*02 (OR = 8.09, 95% CI= [1.91, 36.74]) were risk factors for atopic symptoms in children at one year follow-up. Conclusion: Although, no allergen-specific IgE data were found in infants, we suggest that HLA-DQB1*02 and maternal atopy are important risk factors for atopic symptoms in early stage of childhood. Elucidating this interaction at the molecular level may allow for more targeted treatment and prevention of atopic diseases.