Vascular endothelial growth factor gene polymorphisms in Japanese patients with sarcoidosis.
OBJECTIVE
Vascular endothelial growth factor (VEGF) promotes angiogenesis, mediates vascular permeability, and activates and recruits monocytes. VEGF is produced in activated alveolar macrophages, in epithelioid cells, and in multinuclear giant cells of pulmonary sarcoid granulomas. Recent reports have shown that a polymorphism at - 627 of the VEGF gene is related to VEGF protein production, and a polymorphism at + 813 is associated with VEGF plasma levels. We investigated the roles of such polymorphisms in the development and extent of sarcoidosis.


METHODS
We examined polymorphisms of the VEGF gene in 103 Japanese patients with sarcoidosis and 146 healthy Japanese control subjects. The position - 627 polymorphism was determined using the TaqMan (TaqMan Laboratory, University of Pittsburgh Cancer Institute; Pittsburgh, PA) polymerase chain reaction (PCR) method. For genotyping of the position + 813 polymorphism, the PCR restriction fragment length polymorphism method was performed.


RESULTS
As for + 813 genotypes, the less-common genotypes CT and TT were found more often in control subjects than in patients (odds ratio, 0.490; 95% confidence interval, 0.276 to 0.868). A significant increase in the frequency of the T allele (p = 0.005, Pc = 0.020 after Bonferroni correction) was observed in control subjects. As for - 627 genotypes, the mean value of the FEV(1)/FVC percentage in GG type was lower than that in CC or CG type, however, the other clinical findings did not suggest airway diseases in the GG type.


CONCLUSIONS
We suggest that in VEGF gene polymorphisms the T allele at + 813 may decrease susceptibility to sarcoidosis.
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
Kazuaki
K
Morohashi
Toshinori
T
Takada
Kentaro
K
Omori
Eiichi
E
Suzuki
Fumitake
F
Gejyo
D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000235:genetics* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014797:Vital Capacity
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors