title: Asthma phenotypes in Japanese adults - their associations with the CCL5 and ADRB2 genotypes.
abstract: BACKGROUND
  Cluster analyses were previously performed to identify asthma phenotypes underlying asthma syndrome. Although a large number of patients with asthma develop the disease later in life, these previous cluster analyses focused mainly patients with younger-onset asthma.
  
  
  METHODS
  Cluster analysis examined the existence of distinct phenotypes of late-onset asthma in Japanese patients with adult asthma. We then associated genotypes at the CCL5, TSLP, IL4, and ADRB2 genes with the clusters of asthma identified.
  
  
  RESULTS
  Using the 8 variables of age, sex, age at onset of the disease, smoking status, total serum IgE, %FEV(1), FEV(1)/FVC, and specific IgE responsiveness to common inhaled allergens, two-step cluster analysis of 880 Japanese adult asthma patients identified 6 phenotypes: cluster A (n = 155): older age at onset, no airflow obstruction; cluster B (n = 170): childhood onset, normal-to-mild airflow obstruction; cluster C (n = 119): childhood onset, the longest disease duration, and moderate-to-severe airflow obstruction; cluster D (n = 108): older age at onset, severe airflow obstruction; cluster E (n = 130): middle-age at onset, no airflow obstruction; and cluster F (n = 198): older age at onset, mild-to-moderate airflow obstruction. The CCL5-28C>G genotype was significantly associated with clusters A, B and D (OR 1.65, p = 0.0021; 1.67, 0.018; and 1.74, 0.011, respectively). The ADRB2 Arg16Gly genotype was also associated with clusters B and D (OR 0.47, p = 0.0004; and 0.63, 0.034, respectively).
  
  
  CONCLUSIONS
  The current cluster analysis identified meaningful adult asthma phenotypes linked to the functional CCL5 and ADRB2 genotypes. Genetic and phenotypic data have the potential to elucidate the phenotypic heterogeneity and pathophysiology of asthma.
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Hironori
authors.initials: H
authors.lastname: Masuko
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
authors.forename: Takashi
authors.initials: T
authors.lastname: Naito
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yatagai
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Yamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D018946:Chemokine CCL5 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018946:Chemokine CCL5; D018343:Receptors, Adrenergic, beta-2