Prevalence of tumor necrosis factor-alpha and angiotensin converting enzyme polymorphisms in mild moderate and fatal/near-fatal asthma

Allele 2 of the polymorphism at position -308 in the promoter of the tumor necrosis factor alpha (TNF-alpha) gene, and the D allele of the angiotensin converting enzyme (ACE) gene, have been associated with asthma. We hypothe sized that genotypes containing these alleles would show an increased preva lence in asthmatic as compared with nonasthmatic individuals, and would be associated with asthma severity. Polymerase chain reaction-based assays wer e developed to determine TNF-alpha and ACE genotypes among subjects with mi ld/moderate asthma (n = 92), fatal/near-fatal asthma (n = 159), no asthma ( n = 43), and random population controls (n = 252). The TNF-alpha -308 polym orphism was increased in both subjects with mild/moderate (p = 0.03) and th ose with fatal/near fatal asthma (p = 0.02) versus those without asthma, an d in all subjects with asthma versus random population controls (p = 0.02). The mild/moderate group was subdivided into subjects with mild (n = 43) an d those with moderate (n = 33) asthma. TNF-alpha -308 was increased in the moderately asthmatic versus the nonasthmatic subjects (p = 0.003), and in t he mildly asthmatic subjects (p = 0.01). However, TNF-alpha -308 was not si gnificantly more prevalent in the fatal/near-fatal than in the mild/moderat e asthmatic group. The ACE-D allele did not show an association with either asthma or asthma severity. We conclude that the TNF-alpha -308 polymorphis m may be a risk factor for asthma but does not increase the risk of a fatal or a near-fatal asthma attack, whereas the ACE polymorphism is not associa ted with asthma in this population.