Chest
Volume 123, Issue 5, May 2003, Pages 1520-1526
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Clinical Investigations
SARCOIDOSIS
Vascular Endothelial Growth Factor Gene Polymorphisms in Japanese Patients With Sarcoidosis

https://doi.org/10.1378/chest.123.5.1520Get rights and content

Objectives:

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 FEV1/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.

Section snippets

Subjects

One hundred three patients were recruited from the clinic at the Niigata University Hospital. Sarcoidosis was diagnosed on the basis of the typical features and the presence of epithelioid cell granulomas in biopsy specimens from the lung, skin, or lymph nodes. Forty-one of the patients were men, and 62 were women. All patients in the study were Japanese. The average age of patients at diagnosis was 45.1 years (range, 19 to 74 years). One hundred forty-six healthy subjects who had requested

Results

Allele frequencies and genotypes for VEGF SNPs are summarized in Table 3. The genotype frequencies were in agreement with the Hardy-Weinberg equilibrium (p > 0.1 for all analyses). As for − 627 genotypes, of the 103 patients with sarcoidosis, 41 patients had the CC genotype (39.8%), 43 patients had the CG genotype (41.8%), and 19 patients had the GG type (18.4%). The frequency of C allele was 60.7%. Of the 146 healthy control subjects, 51 subjects were type CC (34.9%), 60 subjects were type CG

Discussion

In this study, we investigated two VEGF SNPs to see whether the polymorphisms are associated with susceptibility to sarcoidosis in the Japanese population. We found a significant difference in the allele frequency at locus + 813 between healthy control subjects and patients with sarcoidosis. Compared with the most common C allele, the less common T allele was underrepresented in the sarcoidosis patient population, suggesting that polymorphism at + 813 is associated with decreased risk for

ACKNOWLEDGMENT

The authors thank Ms. Takeuchi and Ms. Ikeda for help in extracting DNA from clinical specimens.

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