Table 1.
Chromosomal localization and possible function of candidate genes in asthma, and related phenotypes
| Chromosomal region | Population example | Candidate gene | Function | Phenotype |
|---|---|---|---|---|
| 2q14 | German, Italian | IL1 gene family (Gohlke et al., 2004) | Influencing inflammatory response | Asthma, atopy |
| Australian, British | DPP10 (Allen et al., 2003) | Regulation of chemokines and cytokines | Asthma, high IgE | |
| 2q33 | English, Dutch, Norwegian | CTLA4 (Munthe-Kaas et al., 2004) | Regulator of T-cell activation and differentiation | Asthma, high IgE |
| 5q31–q33 | Amish, German, USA white, USA Hispanic, Chinese, Koreans | IL4, IL13, CSF2 (Kabesch et al., 2003; Chen et al., 2004) | IgE isotype switching, induction of Th2 response | High IgE, asthma, AHR |
| IL5 (Namkung et al., 2007) | Eosinophil activation, maturation | Asthma | ||
| IL9 (Temann et al., 2007) | Role in T-, B- and mast cell functions | Asthma | ||
| SPINK5 (Walley et al., 2001) | Possible epithelial differentiation | Atopy, asthma | ||
| CD14 (Vercelli et al., 2001; Leung et al., 2003) | Bacterial LPS binding receptor | High IgE, atopy | ||
| HAVCR1, HAVCR2 (earlier TIM1, TIM3) (McIntire et al., 2004) | Th1, Th2 differentiation | Asthma | ||
| ADRB2 (D'amato et al., 1998; Liggett, 2003) | Influencing the effect of β2-agonists and smoking | Asthma | ||
| Leukotriene C4 synthase (Kedda et al., 2004) | Enzyme for leukotriene synthesis | Aspirin-intolerant asthma, asthma | ||
| CYFIP2 (Noguchi et al., 2005) | Increases adhesion properties of CD4+ cells | Asthma | ||
| 5p13 | German, Hutterites | ZFR, NPR3, ADAMTS12 PRLR, IL7R, LIFR, PTGER4 (Kurz et al., 2006) | Diverse functions | Asthma, BHR |
| 6p21.3 | USA white Dutch, Chinese, Japanese | HLA-D (Marsh et al., 1989; Cookson, 1999) | Antigen presentation | Specific IgE |
| HLA-G (Nicolae et al., 2005 | Immunoregulation | Asthma, BHR | ||
| TNF (Tölgyesi et al., 2006) | Proinflammatory cytokine | Asthma | ||
| LTA (Migita et al., 2005) | Induces the expression of cell adhesion molecules and cytokines | Asthma | ||
| 7p | Finnish, Canadian, Australian | GPRA (Laitinen et al., 2004) | Unknown | Asthma, atopy |
| 11q13 | Australian whites and aborigine, Chinese | MS4A2 (Shirakawa et al., 1994; Hill et al., 1995; Hill and Cookson, 1996) | High-affinity IgE receptor | Atopy, asthma |
| SCGB1A1 (CC16) (Laing et al., 2000) | Regulation of airway inflammation | Asthma | ||
| Japanese | CHRM1 (Maeda et al. 2006) | Airway constriction and inflammation, epithelial cell proliferation | Asthma | |
| 11p | ETS2, ETS3 (Brooks-Wilson, 1999) | Transcription factors | Asthma | |
| 12q14.3–q24.31 | Caucasian, Japanese, Indian, Taiwanian | INFG (Nagarkatti et al., 2002; Wang et al., 2006) | Inhibition of IL-4 activity | Asthma, atopy, high IgE |
| KIT ligand (Sutcliffe et al., 2006) | IL-4 production, mast cell maturation | |||
| STAT6 (Gao et al., 2004; Schedel et al., 2004) | Cytokine-regulated transcription factor | |||
| NOS1 (Grasemann et al., 2000; Shao et al., 2004) | NO: vasodilation, inflammatory regulation | Asthma | ||
| 12q24.21–q24.33 | Danish | SFRS8 (Brasch-Andersen et al., 2006) | Regulation of the splicing of CD45 | Asthma |
| 13q | Australian, British | PHF11, (SETDB2, RCBTB1(?)) (Zhang et al., 2003) | Transcriptional regulation (?) | High IgE |
| 14q22.1–24 | USA white and black | PTGDR (Oguma et al., 2004) | T-cell chemotaxis | Asthma |
| Mexican | Arginase 2 (Li et al., 2006) | Inhibition of NO generation | Asthma | |
| 16p21 | Chinese, German, Spanish | IL4R (Hytonen et al., 2004) | α subunit is part of the receptor for IL-4 and IL-13 | Atopy, asthma |
| 17q11.2–q21 | Hungarian, Korean | RANTES (CCL5) (Yao et al., 2003), MCP-1 (CCL2) (Szalai et al., 2001), eotaxins (CCL11 and CCL24) (Shin et al., 2003; Chang et al., 2005) | Attracting and stimulating of leukocytes | Asthma |
| British, German | ORMDL3 (Moffatt et al., 2007) | Unknown | Asthma | |
| 20p13 | USA white, English, German, Japanese | ADAM33 (Van Eerdewegh et al., 2002) | Possible role in bronchial contractility or remodelling | Asthma, AHR |
Abbreviations: ADAM33, A disintegrin and metalloproteinase domain 33; ADAMTS12, A disintegrin and metalloproteinase domain with thrombospondin type 1 motif 12; ADRB2, β2 adrenergic receptor; AHR, airway hyper-responsiveness; BHR, bronchial hyper-responsiveness; CC16, Clara cell protein 16 or uteroglobin; CHRM1, cholinergic receptor muscarinic-1; CSF2, colony-stimulating factor 2 (granulocyte-macrophage); CTLA4, cytotoxic T-lymphocyte antigen 4; CYFIP2, cytoplasmic fragile X mental retardation protein-interacting protein 2; DPP10, dipeptidyl peptidase 10; ETS, epithelium-specific transcription factor; GPRA, G-protein-coupled receptor for asthma susceptibility; HAVCR, hepatitis A virus cellular receptor; HLA, human leukocyte antigen; Ig, immunoglobulin; IL, interleukin; IL7R, IL-7 receptor; INF, interferon; LIFR, leukemia inhibitory factor receptor; LPS, lipopolysaccharide; LTA, lymphotoxin-α; MCP-1, monocyte chemoattractant protein-1; MHC, major histocompatibility complex; MS4A2, membrane-spanning 4 domains, subfamily A, member 2 (high-affinity IgE receptor β subunit); NOS1, neuronal nitric oxid synthase; NPR3, natriuretic peptide receptor C; PHF11, plant homeodomain finger protein-11; PRLR, prolactin receptor; PTGDR, prostaglandin D2 receptor; PTGER4, prostaglandin E4 receptor; RANTES, regulated on activation normal T-cell expressed and secreted; SCF, stem cell factor; SFRS8, splicing factor, arginine/serine-rich 8; STAT6, signal transducer and activator of transcription 6; TIM, T-cell integrin mucin-like receptor; TNF, tumor necrosis factor-α; ZFR, zinc-finger RNA-binding protein.