Polymorphism of Clara cell 10-kD protein gene of sarcoidosis.
Clara cell 10-kD protein (CC10) exhibits potent antiinflammatory properties. G38A polymorphism was found in the CC10 gene. We investigated the genetic influence of the allele on the development of sarcoidosis using case control analysis in a Japanese population (265 sarcoidosis cases and 258 control subjects). The A allele frequency in sarcoidosis cases (45.1%) was significantly higher than healthy control subjects (34.9%, p = 0.0002). According to outcomes, we divided 223 patients with follow-up periods of 3 years or more into two subgroups (55 progressive and 168 regressive disease). The A allele frequency in patients with progressive disease was significantly higher than control subjects (odds ratio = 4.55; 95% confidence interval, 2.97-6.97; p < 0.0001), whereas that of regressive disease was not. The A/A genotypes had significantly lower bronchoalveolar lavage fluid CC10 levels than the G/G (nonsmokers, p = 0.0054, and smokers, p = 0.0045) and G/A genotypes (nonsmokers, p = 0.0022, and smokers, p = 0.0402). The reporter gene assay showed significantly lower reporter activities in the presence of interferon-gamma for the 38A construct than the 38G construct (p = 0.0177). The G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis.
Ohchi
Takashi
T
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Shijubo
Noriharu
N
Kawabata
Isao
I
Ichimiya
Shingo
S
Inomata
Shin-ichiro
S
Yamaguchi
Akihiro
A
Umemori
Yoshifumi
Y
Itoh
Yoshihisa
Y
Abe
Shosaku
S
Hiraga
Yomei
Y
Sato
Noriyuki
N
D019943:Amino Acid Substitution; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D017565:Sarcoidosis, Pulmonary / Q000235:genetics* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects; D014598:Uteroglobin
D011506:Proteins; C556389:SCGB1A1 protein, human; D014598:Uteroglobin