Association of polymorphisms in vascular endothelial growth factor gene with the age of onset of amyotrophic lateral sclerosis

This study investigated the association between polymorphisms in vascular endothelial growth factor (VEGF) gene (‐1558C‐T, ‐1190A‐G and ‐1154A‐G) and age at onset of amyotrophic lateral sclerosis (ALS). Between July 2000 and June 2004 we conducted a clinical genetic study at Peking University Third Hospital, China. The analyses included a total of 93 ALS patients. Genotyping was performed by using the 5′‐nuclease assay technology (Applied Biosystems) with TaqMan® allele‐specific fluorogenic oligonucleotide probes. We used multivariate linear regression modelling and haplotype‐based association test to analyse the association of VEGF gene polymorphisms with the age of onset, adjusting for initial symptoms and sex. The results indicated that patients with the ‐1190A/G and ‐1190G/G genotypes exhibited about a 4.1‐ and 9.4‐years earlier onset of ALS than the patients with the ‐1190A/A genotype. A similar pattern emerged when the VEGF ‐1154A‐G gene was considered: the β was −7.9(p<0.001) years and −11.7(p<0.001) years for ‐1154A/G and ‐1154G/G genotypes, respectively. The VEGF ‐1558C‐T had a positive effect in the ‐1558C/T group (p = 0.007, β = 7.0) and ‐1558T/T (p<0.001, β = 9.6) compared to the ‐1558C/C group. We neither observed an interaction nor haplotype association with age onset among ‐1558C‐T, ‐1190A‐G and ‐1154A‐G. In conclusion, our results indicate, for the first time, that there was an important association between the polymorphism of the VEGF gene and age of ALS onset. This suggests a possible role for VEGF variability in the aetiology of individual differences in ALS onset.