title: Association of polymorphisms in vascular endothelial growth factor gene with the age of onset of amyotrophic lateral sclerosis.
abstract: 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 beta 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, beta = 7.0) and -1558T/T (p<0.001, beta = 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.
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Peking University, Beijing, China.
authors.forename: Dafang
authors.initials: D
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Aili
authors.initials: A
authors.lastname: Lu
authors.forename: Huagang
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Yingshuang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Shui
authors.forename: Linsong
authors.initials: L
authors.lastname: Li
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D004247:DNA