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Background: Leukotrienes (LTs) have been identified as central mediators in asthma and allergy. Pharmacological inhibition of cysteinyl-LT activity improves asthma symptoms and control. Accumulating evidence suggests a role for the dihydroxy leukotriene LTB4 in airway disease. LTA4 hydrolase and 5-lipoxygenase activating protein have key roles in LTB4 production. Single nucleotide polymorphism (SNPs) and haplotypes spanning the LTA4H and ALOX5AP genes have been associated with LTB4 production and myocardial infarction (MI). Objective: To assess the contribution of LTA4H and ALOX5AP polymorphism to asthma and allergy susceptibility. Methods: Three hundred and forty-one Caucasian families (two asthmatic siblings) were genotyped for eight SNPs spanning ALOX5AP and five SNPs spanning LTA4H. Association analyses of asthma and related phenotypes (total IgE, atopy, bronchial hyper-responsiveness, FEV1) were undertaken using the Family Based Association Test. Results: Single point analyses identified association ( P < 0.05) between SNPs SG13S114, SG13S89, SG13S41 ( ALOX5AP), rs1978331 ( LTA4H) and asthma and/or related phenotypes. Haplotype analyses using all LTA4H SNPs identified a single key risk haplotype for the development of asthma ( P = 0.006) and related phenotypes ( P = 0.042–0.005). Haplotype analyses using all ALOX5AP SNPs identified several asthma and atopy risk and protective haplotypes. There was limited correlation with previously identified MI risk haplotypes in both genes. Carriers of both ALOX5AP SG13S41 and LTA4H rs1978331 alleles had an increased risk of developing asthma (OR 2.17, CI 1.41–3.32). Conclusions: These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility in the Caucasian population and support a role for LTB4 in disease pathogenesis. [ABSTRACT FROM AUTHOR]

The article offers information on the statistics of atopy and atopic disease susceptibility and chromosome 19q13 based on the studies conducted independently in Great Britain. It informs that the first study analyses the Southampton asthma sibling pair cohort which has been described as using total IgE, elevated specific IgE and positive skin prick test. It reports that chromosome 19q13 contains an atopy susceptibility locus.

Background: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5-15% of the exposed population suggesting an underlying genetic susceptibility., Methods: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects., Results: Neither the distribution of HLA class I antigens nor the distribution of TNF-alpha A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects., Conclusions: These results suggest that HLA class I antigens and TNF-alpha A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.