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 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.
Chen
Dafang
D
Department of Epidemiology and Statistics, School of Public Health, Peking University, Beijing, China.
Shen
Li
L
Wang
Liping
L
Lu
Aili
A
Zhang
Huagang
H
Zhang
Xiaoyan
X
Zhang
Yingshuang
Y
Shui
Wei
W
Li
Linsong
L
Fan
Dongsheng
D
Zhang
Jun
J
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*
D042461:Vascular Endothelial Growth Factor A; D004247:DNA