title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pgao1@jhmi.edu
authors.forename: Pei-Song
authors.initials: PS
authors.lastname: Gao
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: Beverly
authors.initials: B
authors.lastname: Plunkett
authors.forename: Alkis
authors.initials: A
authors.lastname: Togias
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006506:Hepatitis A / Q000097:blood; D035922:Hepatitis A Antibodies / Q000097:blood; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009077:Mucins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011991:Receptors, Virus / Q000235:genetics; D016036:Seroepidemiologic Studies; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C491143:HAVCR1 protein, human; C448908:HAVCR2 protein, human; D035922:Hepatitis A Antibodies; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009077:Mucins; D011991:Receptors, Virus