title: Clinical relevance of vascular endothelial growth factor type A (VEGFA) and VEGF receptor type 2 (VEGFR2) gene polymorphism in chronic lymphocytic leukemia.
abstract: Vascular endothelial growth factor type A (VEGFA) is a key regulator of angiogenesis and vascular permeability. Chronic lymphocytic leukemia (CLL) cells are able to secrete VEGFA and express VEGFA receptors, thus it can be hypothesized that VEGFA-mediated signaling influences CLL clone survival. In this case-control study we verified whether inherited differences in activities of VEGFA and its main receptor VEGFR2 impact predisposition to CLL or the course of the disease. Four functional single nucleotide polymorphisms (SNPs) including two SNPs in VEGFA gene, namely rs2010963 (+405G>C) and rs3025039 (+936C>T) and two SNPs in VEGFR2 gene including rs7667298 (-271G>A) and rs1870377 (+1719A>T) were genotyped using PCR-based assays in 223 Caucasian CLL patients and 150 matched controls. Regarding VEGF rs2010963 SNP, we observed an association between CLL and allele C distribution with an OR of 1.52 (95% CI, 1.002-2.312), p=0.04. The distribution of other genotypes and alleles was similar in CLL and control groups. No genotype or allele was significantly associated with important prognostic factors in CLL including clinical stage, IgVH mutational status, ZAP-70 expression and FISH cytogenetic abnormalities. In conclusion, the results of our study indicate that genetic polymorphisms in VEGFA mediated pathway may influence the susceptibility to CLL.
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland. Electronic address: joannagora@op.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Góra-Tybor
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jamroziak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D044465:White People; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human
keywords: Angiogenesis; CLL; Polymorphism; VEGFA; VEGFR2