Genetic Risk Factors for Psoriasis in Turkish Population: −1540 C/A, −1512 Ins18, and +405 C/G Polymorphisms within the Vascular Endothelial Growth Factor Gene
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Background: Evidence regarding the vascular endothelial growth factor A (VEGFA) as a potent mediator of angiogenesis and inflammation in psoriasis has revealed variations in this gene as surrogate markers of psoriasis. Objective: VEGFA gene polymorphisms (−1540 C/A, −1512 Ins18, −460 T/C, and +405 C/G) in psoriasis susceptibility in Turkish population were investigated. Methods: A total of 200 age, sex and ethnicity-matched psoriatic and healthy individuals were examined for clinical type, response to therapy, serum VEGFA and its receptor levels, genotypes and haplotypes. Results: The +405 GG, +405 CG, −1540 CA, and −1512 +Ins18 genotypes conferred a significant risk for developing psoriasis. The C-InsTC haplotype in the controls and C+InsTG, A+InsTC, and A-InsTG haplotypes in psoriatic patients were observed to be significantly high. Increased serum levels of VEGFA were detected in psoriatic patients with the C-InsTC haplotype than that in the controls. The +405 GG genotype was significantly more frequent in psoriatic patients with a positive family history, and the moderate form of psoriasis was more frequent among C+InsTG haplotype carriers than that among the other patients. The +405 GG genotype was found to be more frequent in patients responding to oral retinoids. Serum VEGFR1/FLT1 and VEGFR2/KDR levels were not significantly different when psoriatic patients and controls were stratified based on the risk polymorphic variants. Conclusion: VEGFA gene +405 GG and CG, −1512+Ins18, and −1540 CA genotypes are associated with an increased risk of psoriasis in Turkish population. The G allele at +405 and an 18-bp insertion at −1512 are primarily the risk factors for psoriasis, and this risk is potentiated by the presence of the A allele at the −1540 locus.
Abstract
Background: Evidence regarding the vascular endothelial growth factor A (VEGFA) as a potent mediator of angiogenesis and inflammation in psoriasis has revealed variations in this gene as surrogate markers of psoriasis. Objective: VEGFA gene polymorphisms (−1540 C/A, −1512 Ins18, −460 T/C, and +405 C/G) in psoriasis susceptibility in Turkish population were investigated. Methods: A total of 200 age, sex and ethnicity-matched psoriatic and healthy individuals were examined for clinical type, response to therapy, serum VEGFA and its receptor levels, genotypes and haplotypes. Results: The +405 GG, +405 CG, −1540 CA, and −1512 +Ins18 genotypes conferred a significant risk for developing psoriasis. The C-InsTC haplotype in the controls and C+InsTG, A+InsTC, and A-InsTG haplotypes in psoriatic patients were observed to be significantly high. Increased serum levels of VEGFA were detected in psoriatic patients with the C-InsTC haplotype than that in the controls. The +405 GG genotype was significantly more frequent in psoriatic patients with a positive family history, and the moderate form of psoriasis was more frequent among C+InsTG haplotype carriers than that among the other patients. The +405 GG genotype was found to be more frequent in patients responding to oral retinoids. Serum VEGFR1/FLT1 and VEGFR2/KDR levels were not significantly different when psoriatic patients and controls were stratified based on the risk polymorphic variants. Conclusion: VEGFA gene +405 GG and CG, −1512+Ins18, and −1540 CA genotypes are associated with an increased risk of psoriasis in Turkish population. The G allele at +405 and an 18-bp insertion at −1512 are primarily the risk factors for psoriasis, and this risk is potentiated by the presence of the A allele at the −1540 locus.
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