title: Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk.
abstract: Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells.
authors.affiliation: Department of Internal Medicine, Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Bucheon Hospital, Jung Dong, Wonmi Ku, Gyeonggi Do, Korea.
authors.forename: Eun Kyong
authors.initials: EK
authors.lastname: Shin
authors.forename: Shin-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Cho
authors.forename: Seok
authors.initials: S
authors.lastname: Jung
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Yoon
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Soo Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yang Ki
authors.initials: YK
authors.lastname: Kim
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Choi
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000483:Alleles; D001249:Asthma / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D016186:Receptor, Macrophage Colony-Stimulating Factor