Abstract |
Surfactant protein D (SFTPD) induces emphysema in knockout mice, but the association of SFTPD with chronic obstructive pulmonary disease ( COPD) and emphysema in humans is unclear. Therefore, we aimed to determine the association between genetic variations in SFTPD and susceptibility to COPD and emphysema.Two populations were studied: population A comprised 270 smokers, including 188 COPD and 82 at-risk subjects, and population B comprised 1131 autopsy cases including 160 cases with emphysema. Six single-nucleotide polymorphisms (SNPs) that tagged the linkage disequilibrium blocks on the entire SFTPD gene were genotyped; the associations of the genotypes with COPD, pulmonary function, percentage of the low-attenuation area (LAA%), and percentage of the airway wall area (WA%) were determined in population A. In population B, the associations of the genotypes with emphysema were assessed.A C allele at SNP rs721917 that results in the replacement of Met with Thr at position 11 in SFTPD was positively correlated with the LAA% in the upper lung (P = 1.1 × 10(-5)) and overall LAA% (P = 1.0 × 10(-4)), and negatively correlated with the serum concentration of SFTPD (P = 7 × 10(-11)) in the population A. The C/C (rs721917/rs10887199) haplotype was associated with emphysema in both the populations.Subjects with a C allele at rs721917 have a lower serum SFTPD concentration and are more susceptible to emphysema. This suggests a protective effect of SFTPD against COPD and emphysema.
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Authors | Takeo Ishii, Koichi Hagiwara, Koichiro Kamio, Shinobu Ikeda, Tomio Arai, Makiko Naka Mieno, Toshio Kumasaka, Masaaki Muramatsu, Motoji Sawabe, Akihiko Gemma, Kozui Kida |
Journal | European journal of human genetics : EJHG
(Eur J Hum Genet)
Vol. 20
Issue 2
Pg. 230-5
(Feb 2012)
ISSN: 1476-5438 [Electronic] England |
PMID | 21934714
(Publication Type: Journal Article)
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Chemical References |
- Pulmonary Surfactant-Associated Protein D
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Topics |
- Aged
- Aged, 80 and over
- Alleles
- Emphysema
(etiology, genetics)
- Female
- Genetic Association Studies
- Humans
- Linkage Disequilibrium
- Male
- Middle Aged
- Phenotype
- Polymorphism, Single Nucleotide
- Pulmonary Disease, Chronic Obstructive
(complications, genetics)
- Pulmonary Surfactant-Associated Protein D
(blood, genetics)
- Risk Factors
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