Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults

Background: Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. However, association studies with interleukin-4 (IL-4), IL-4 receptor alpha subunit (IL- 4R alpha), tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were inconclusive, as both positive and negative results were obtained in several populations studied. We aimed to investigate the association of the polymorphisms for IL- 4 (C-589T), IL-4R alpha (Gln576Arg), TNF-alpha (G-308A) and LT-alpha (A252G) genes as candidates and asthma in adult Hong Kong Chinese population. Methods: The association study was conducted in an age-and smoking status-matched case-control design in asthma patients (n = 292) and healthy controls (n = 292) using polymerase chain reaction and restriction fragment length polymorphism. Results: No significant differences were found in allele and genotype frequencies of all four genes between patients and controls. After stratification by atopic status, the heterozygous AG genotype of LT-alpha (A252G) was found to increase risk of asthma in atopic population [ odds ratio ( OR) = 2.00, 95% CI 1.09 - 3.67, p = 0.024]. When stratified by smoking status, we found increased risk of asth-ma with subjects carrying the heterozygous AG and homozygous GG genotypes of LT-alpha in ever-smokers (OR = 2.73, 95% CI 1.11 - 6.69, p = 0.028 for heterozygotes; OR = 3.34, 95% CI 1.16 - 9.62, p = 0.026 for homozygotes). Conclusion: Our results suggest that the variability of LT-alpha genotypes may have potential implications for individual susceptibility to asthma in atopic or in ever-smoking Chinese adults in Hong Kong. Copyright c 2007 S. Karger AG, Basel.