Lack of association between VEGF polymorphisms and ALS in a Dutch population

Abstract

Sequence alterations in the promoter region of the vascular endothelial growth factor (VEGF) gene have been implicated in increasing the risk of developing ALS. VEGF promoter haplotypes were determined in 373 patients with sporadic ALS and 615 matched healthy controls in The Netherlands. No significant association between the previously reported at-risk haplotypes and ALS was found. Pooling our results with the previously studied population still showed a significant association with the AAG haplotype.

Large-scale SOD1 mutation screening provides evidence for genetic heterogeneity in amyotrophic lateral sclerosis

“…For instance, polymorphisms in the promoter region of the vascular endothelial growth factor gene ( VEGF ) are a susceptibility factor in Belgium,30 but not in The Netherlands 31. An SNP in the gene encoding the inositol 1,4,5-trisphosphate receptor type 2 ( ITPR2 ) has been demonstrated to be in association with SALS in two independent Dutch populations and in Sweden, but not in Belgium 32…”

Meta-analysis of vascular endothelial growth factor variations in amyotrophic lateral sclerosis: increased susceptibility in male carriers of the -2578AA genotype

“…In a smaller follow-up association study by Terry et al ,25 individuals homozygous for the “at-risk” variations also exhibited a threefold increased risk of ALS. In contrast, studies performed in a British, Dutch, American and, recently, Italian population reported that there was no association between VEGF haplotypes and SALS 26 27 28 29. A final study30 reported that the role of VEGF in ALS in the German population may depend on gender; however, the results of this study did not entirely confirm the findings of the initial study, as the common −1154G allele, rather than the −1154A risk allele, was associated with female ALS in this study.…”

“…Text words used for the search were: “vascular endothelial growth factor” or “VEGF” in combination with “polymorphism”, “genotype” or “mutation” and with “amyotrophic lateral sclerosis” or “ALS”. Eight of these studies were performed in populations collected in European countries, two were in the USA and one in China 24 25 26 27 28 29 30 31. Almost all studies investigated the −2578C/A and −1154G/A variations in the VEGF promoter and the −634G/C variation in the 5′ untranslated region of the VEGF gene.…”

VEGF genetic variability is associated with increased risk of developing Alzheimer's disease

“…In ALS patients, fewer motor neurons express normal levels of VEGF and its receptor VEGFR-2 and haplotypes of 3 genetic variations in the VEGF gene (−2578CNA, rs699947; −1154GNA, rs1570360; −634GNC, rs 2010963), producing low levels of VEGF, increased the risk of sporadic ALS (SALS) in four distinct European populations from Sweden, England and Belgium [13]. However, subsequent studies performed within British, Dutch, American and Italian populations reported that there was no association between VEGF gene variability and SALS [14][15][16].…”