Objective The transforming growth factor beta-1 gene (TGFB1) is one of the most promising candidate genes for chronic obstructive pulmonary disease (COPD). Several case-control studies have been performed and generated inconsistent results. The possible reasons for these discrepancies include the diversity of ethnic populations and the heterogeneity of COPD, including emphysema and airway disease. We designed this study to investigate the association of single nucleotide polymorphisms (SNPs) of TGFB1 with the emphysema phenotype in the Japanese population.
Methods Eight SNPs in TGFB1 (rs2241712, rs1982072, and rs1800469 in the promoter region; rs1982073 in exon 1; rs2241716 and rs4803455 in intron 2; rs6957 and rs2241718 in the 3' region) were genotyped by allelic discrimination assays in 70 COPD patients with emphysema phenotype and 99 healthy smokers. The emphysema phenotype was identified by high-resolution computed tomography imaging using Goddard's method.
Results The frequency of one significant haplotype structured by the eight SNPs was significantly higher in the emphysema group (10%) than in the healthy smokers (4%, p=0.02). In the emphysema group, the predicted value of forced expiratory volume in 1 second after bronchodilator administration was significantly associated with the minor alleles of the two SNPs (rs1800469 and rs1982073, p=0.007 and 0.032, respectively), however, the low attenuation area and carbon monoxide diffusing capacity were not associated with the SNPs. In addition, the rs1800469T and rs1982073C alleles were significantly more prevalent in patients with severe and very severe airflow limitation than in those with mild and moderate airflow limitation (p=0.007 and 0.041, respectively).
Conclusions One significant haplotype of TGFB1 is associated with the emphysema phenotype in the Japanese population. Two TGFB1 SNPs (rs1800469 and rs1982073) are associated with the severity of COPD in patients with emphysema phenotype.