title: Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms.
abstract: BACKGROUND
  Surfactant protein A (SP-A) and SP-D are clinically established in Japan as serum biomarkers for diagnosing interstitial lung diseases (ILDs). Serum SP-D levels are affected by genetic variants. We conducted the present study to examine whether serum SP-A and/or SP-D levels in healthy subjects (HS) and patients with ILDs differ between populations with different genetic backgrounds.
  
  
  METHODS
  German subjects (n = 303; 138 patients with idiopathic interstitial pneumonias [IIPs] and 165 HS) and Japanese subjects (n = 369; 94 patients with IIPs and 275 HS) were enrolled. Serum SP-A and SP-D levels were measured using an enzyme-linked immunosorbent assay, and four single-nucleotide polymorphisms (SNPs) in the SFTPD gene were genotyped using genomic DNA extracted from blood samples.
  
  
  RESULTS
  In both the German and Japanese cohorts, serum SP-A and SP-D levels were significantly higher in patients with IIPs than in HS. There were no significant differences in SP-A levels between the German and Japanese cohorts; however, we found that serum SP-D levels were significantly higher in the German cohort, both in patients with IIPs and in HS (p < 0.001 and p = 0.005, respectively). Furthermore, the genotype distributions of the four SNPs in the SFTPD gene (rs721917, rs1998374, rs2243639, and rs3088308) were significantly different between German and Japanese cohorts (p < 0.001, p < 0.001, p = 0.022, and p < 0.001, respectively), and univariate linear regression analyses revealed that the genotypes of rs721917, rs1998374, and rs2243639 significantly correlated with serum SP-D levels (p < 0.001, p < 0.001, and p = 0.011, respectively). Furthermore, multivariate analyses revealed that the genotypes of these three SNPs correlated independently with serum SP-D levels (p < 0.001, p = 0.001, and p = 0.038, respectively), whereas ethnicity did not significantly correlate with serum SP-D levels.
  
  
  CONCLUSIONS
  In patients with IIPs and HS, serum SP-D, but not SP-A, levels were significantly higher in the German than in the Japanese cohort, in part, because of the different frequencies of SFTPD gene polymorphisms.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horimasu
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. nhattori@hiroshima-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Sonosuke
authors.initials: S
authors.lastname: Tanaka
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonella
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ohshimo
authors.forename: Josune
authors.initials: J
authors.lastname: Guzman
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005858:Germany; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000097:blood / Q000235:genetics; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide; D037662:Pulmonary Surfactant-Associated Protein A / Q000097:blood; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood* / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D