MUC7 polymorphisms are associated with a decreased risk of a diagnosis of asthma in an African American population.

Mucin glycoproteins contribute to lung pathophysiology in asthma. The protein backbone of mucin glycoproteins is encoded by specific MUC genes, which exhibit a high degree of polymorphisms that generate a variable number of tandem repeat (VNTR) domains. MUC7 typically encodes for 6 VNTRs, each with 23 amino acids. In a northern European cohort, a polymorphism encoding MUC7*5 (5-VNTR) is in 100% linkage disequilibrium with the single nucleotide polymorphism rs9982010 and associated with a decreased risk of being asthmatic and having better lung function. African Americans have a 5- to 10-fold increase in incidence of asthma relative to whites, who are believed to be partially associated with higher genetic susceptibility. Occurrence of the rs9982010 and MUC7 allelic frequencies was evaluated in inner-city African Americans to test their association with a diagnosis of asthma. Genomic DNA, collected from a cohort of African American asthmatic subjects, was used to detect the MUC7 VNTR polymorphisms and to analyze the rs9982010 single nucleotide polymorphism. A logistic regression analysis showed that the MUC7*5-VNTR allele decreased the likelihood of a diagnosis of asthma (odds ratio, 0.173 [95% confidence interval, 0.041-0.737]; P < 0.018) and is not in a strong linkage disequilibrium with the rs9982010 (r = 0.03; odds ratio, 66; confidence interval, 5.913-736.72). A novel MUC7*4-VNTR polymorphism, identified in an African American nonasthmatic individual, was linked to a structural rearrangement of the VNTR domain. These data extend the association of MUC7*5 allelic polymorphisms and asthma to inner-city African Americans.