Chest
Clinical InvestigationsSARCOIDOSISVascular Endothelial Growth Factor Gene Polymorphisms in Japanese Patients With 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.
References (33)
- et al.
Receptor chimeras indicate that the vascular endothelial growth factor receptor-1 (VEGFR-1) modulates mitogenic activity of VEGFR-2 in endothelial cells
J Biol Chem
(2000) - et al.
Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1
Blood
(1996) - et al.
The vascular endothelial growth factor receptor Flt-1 mediates biological activities: implications for a functional role of placenta growth factor in monocyte activation and chemotaxis
J Biol Chem
(1996) - et al.
The gene polymorphism of tumor necrosis factor-β, but not that of tumor necrosis factor-α, is associated with the prognosis of sarcoidosis
Chest
(2001) - et al.
Novel polymorphisms in the promoter and 5′ UTR regions of the human vascular endothelial growth factor gene
Hum Immunol
(1999) - et al.
Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production
Cytokine
(2000) - et al.
Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma
J Allergy Clin Immunol
(2001) - et al.
VEGF, basic-FGF, and TGF-β in Crohn’s disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation
Am J Gastroenterol
(2001) - et al.
Changes in the peripheral vasculature of various organs in patients with sarcoidosis: possible role of microangiopathy
Heart Vessels
(1986) - et al.
Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis: I. Enhanced capacity of bronchoalveolar lavage cells from patients with pulmonary sarcoidosis to induce angiogenesisin vivo
Am Rev Respir Dis
(1989)
Molecular and biological properties of the vascular endothelial growth factor family of proteins
Endocr Rev
The biology of vascular endothelial growth factor
Endocr Rev
Expression and localization of vascular endothelial growth factor and its receptor flt in pulmonary sarcoidosis
Virchows Arch
Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999
Am J Respir Crit Care Med
Vitamin D receptor gene polymorphism in patients with sarcoidosis
Am J Respir Crit Care Med
CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis
Am J Respir Crit Care Med
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