title: Association of CHI3L1 in African-Americans with prior history of asthma exacerbations and stress.
abstract: BACKGROUND
  Asthma exacerbations are influenced by multiple factors including environmental exposures, psychosocial interactions, and genetic variations.
  
  
  OBJECTIVE
  To better understand the correlation between clinical, physiologic, genetic, and psychological dimensions in asthma phenotypes and exacerbations.
  
  
  METHODS
  Supervised cluster analysis of a previously conducted clinical trial of asthma was used to identify subpopulations with differing exacerbation rates in an African-American study population (n = 475). The clusters were characterized by their clinical characteristics and genetic variations. The genetic analysis (n = 322) compared subgroups across 40 different polymorphisms of 10 genes associated with asthma exacerbations.
  
  
  RESULTS
  Four clusters were identified with varying annualized rates of exacerbations. Cluster 1 (n = 272) was represented by subjects with a mean age of 25 years and 52% females. In contrast, cluster 4, most divergent from cluster 1, was represented by subjects with the highest rate of asthma exacerbations (1.18 events per year), was mostly female (>80%), with a mean body mass index of 34, and was distinguished by the report of stress and emotions as the cause for prior exacerbations. Lower lung function and increased rescue medication use was also reported in cluster 4. Additionally, genetic analysis revealed a significant difference in distribution of genotypes among the four clusters for rs4950928, a single nucleotide polymorphism (SNP) located in the promoter region of the CHI3L1, the chitinase 3-like 1 gene encoding YKL-40.
  
  
  CONCLUSIONS
  African-Americans who reported stress and emotions as a primary historical cause of exacerbations had the highest annualized rate of exacerbation. Further, a significant correlation with the genotypes in CHI3L1/YKL-40 was observed in the context of stress and asthma severity.
authors.affiliation: Respiratory Medcines Development Center, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. hector.g.ortega@gsk.com
authors.forename: Hector
authors.initials: H
authors.lastname: Ortega
authors.forename: Charlene
authors.initials: C
authors.lastname: Prazma
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Suruki
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Wayne H
authors.initials: WH
authors.lastname: Anderson
mesh_terms: D054392:Adipokines / Q000235:genetics* / Q000276:immunology; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000523:psychology*; D000071451:Chitinase-3-Like Protein 1; D016000:Cluster Analysis; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D037102:Lectins / Q000235:genetics* / Q000276:immunology; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D013312:Stress, Physiological / Q000235:genetics* / Q000276:immunology
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D004247:DNA