Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American population.

摘要

Background The T-cell immunoglobulin mucin ( TIM ) proteins and their genetic variants have been suggested to play a role in regulating allergic diseases. Objective Genetic association of the sequence variants for TIM-1 and TIM-3 genes with asthma in an African American population was investigated. Methods Both case-control and family-based association analyses were performed for a total of 7 polymorphisms, including 3 single nucleotide polymorphism (SNPs) and 1 insertion/deletion polymorphism in the TIM-1 and 3 SNPs in the TIM-3 genes. The exposure to hepatitis A virus as judged by seropositivity was also examined. Results In the case-control design, the frequencies of the TT genotype for SNP rs2277025 and the homozygous deletion variant (157delMTTTVP) in the fourth exon of the TIM-1 gene were higher among patients with patients with asthma compared with the controls (odds ratio [OR], 2.779, P = .016; and OR, 3.09, P = .022, respectively). This association was substantiated by haplotype analysis of these and 2 additional SNPs (OR, 2.48; P = .004), and also by family-based tests for the allele and haplotype carrying 157delMTTTVP ( P = .009 and P = .048, respectively). Furthermore, this association seems to exist even in the hepatitis A virus-seronegative subjects in our data. None of the 3 variants in TIM-3 genes yielded significant association with either asthma or asthma-related phenotypes. Conclusion Our findings suggest that the genetic variants of the TIM-1 but not the TIM-3 gene contribute to asthma susceptibility in this African-American population.