Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk

• Published in: Human genetics Vol. 128; no. 3; pp. 293 - 302
• Main Authors: Shin, Eun Kyong, Lee, Shin-Hwa, Cho, Sung-Hwan, Jung, Seok, Yoon, Sang Hyuk, Park, Sung Woo, Park, Jong Sook, Uh, Soo Taek, Kim, Yang Ki, Kim, Yong Hoon, Choi, Jae-Sung, Park, Byung-Lae, Shin, Hyoung Doo, Park, Choon-Sik
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.09.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Alleles; Allergies; Antigens; Asthma; Asthma - etiology; Asthma - genetics; Asthma - immunology; Base Sequence; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Chromosomes; Cytokines; Dendritic cells; DNA; DNA Primers - genetics; Gene Frequency; Gene Function; Genes; Genetic Predisposition to Disease; Genomes; Hospitals; Human Genetics; Humans; Immunity, Innate - genetics; Linkage Disequilibrium; Macrophage colony stimulating factor; Medicine; Metabolic Diseases; Models, Genetic; Molecular Medicine; Monocytes - immunology; Neutrophils; Neutrophils - immunology; Original Investigation; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Receptor, Macrophage Colony-Stimulating Factor - blood; Receptor, Macrophage Colony-Stimulating Factor - genetics; Respiratory diseases; Risk factors; RNA; RNA, Messenger - blood; RNA, Messenger - genetics; Asthmatic Patient; Rare Allele; Asthmatic Subject; Pulmonary Alveolar Proteinosis; Asthma
• ISSN: 0340-6717; 1432-1203; 1432-1203
• DOI: 10.1007/s00439-010-0850-3

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.