Psöriazis'Li Hastalarda Vasküler Endotelyal Büyüme Faktör Polimorfizminin Araştırılması

Abstract

Psoriasis is a chronic, hyperproliferative skin disease. Microvascular changes occur and inflammatory cells are increased in the lesional skin. In studies, high levels of vascular endothelial growth factor (VEGF) have been shown in patients with psoriasis. VEGF gene is known as a polymorphic gene and limited studies exist showing the relationship between VEGF polymorphisms with psoriasis. This study aimed to reveal the relationship between VEGF (+405 C/G), VEGF (-460T/C), VEGF (-1540C/A), VEGF (-1451C/T) and VEGF (-1512Ins18) polymorphisms with psoriasis susceptibility in Turkish population, and analyze the effects of these genetic variations to VEGF, VEGFR-1 (fms-like tyrosine kinase-1, flt-1) and VEGFR-2 (kinase domain region KDR, flk-1) protein levels. For this purpose, whole blood and serum samples were collected from age and sex matched 100 patients with psoriasis and 100 healthy controls. After DNA isolation from whole blood samples, the selected regions were amplified by using ploymerase chain reaction (PCR). PCR products was cut with restriction endonuclease enzymes that are specific for VEGF polymorphisms. Cutting products were carried on agarose gel electrophoresis and individuals were identified as normal, homozygote, heterozygote according to the number of bands. Psoriasis risk assessment was performed using SPSS v21.0 and haplotype analyzes were performed using Haplotype Analysis v1.04 programs. Serum VEGF, VEGFR1, VEGFR2 levels were analyzed with ELISA and their association with haplotypes were statistically evaluated. Being homozygous (GG) and heterozygous (CG) for VEGF (+405 C/G) increased the risk in developing psoriasis by approximately 9 and 7 fold, respectively (ORs=9.40 and 7.02 respectively; p<0.001 for both). High frequency of G allele in patients and high frequency of C allele in controls were observed ( p<0,001). Homozygosity is found increased in the patients with family history (p<0.05). Heterozygote (TC) patients for VEGF (-460 T/C) showed a decreased risk for psoriasis (OR=0,48; p<0,05). Two and a half fold increased risk of psoriasis was observed in heterozgyote (CA) genotype of VEGF (-1540 C/A) (OR=2.5; p<0.001). High frequency of A allele in patients and high frequency of C allele in controls were observed (p<0,002). VEGF (-1512Ins18) polymorphism increased the risk of disease by 4 fold (OR=4.01; p<0.001). The most common haplotype was found as VEGF (+405 GG) + (-1512Ins18) in patients (p<0.001). The presence of haplotype VEGF (405 CC) + (-460 TT) + (-1540 CC) + (-1512 without ins18) was found higher in controls compared to patients (p<0.001). The other common haplotypes in patients were VEGF (+405 CG) + (-1512Ins18); VEGF (+405 GG) + (-1540 CA); VEGF (+405 CG) + (-1540 CA), respectively (p=0.002 for all). The haplotype of VEGF (+405 CG) + (-1540 CA) + (-1512Ins18) was also observed high in patients (p=0.013). Hardy-Weinberg equilibrium was found significantly not provided in the patient (p = 0.002) and control (p <0.001) groups for VEGF (+405 C/D); in patient group (p <0.001) for VEGF (-1512 Ins18) polymorphisms. No significant relationships were detected between haplotypes with the types of disease (Type I - Type II), the severity of disease (PASI) and treatment response in our study. In conclusion, our study showed that VEGF gene polymorphisms can be considered as risk factors for psoriasis in Turkish population. More extensive studies with large sample size are needed to show a clear genetic risk.