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

作者：Chen, Dafang; Shen, Li; Wang, Liping; Lu, Aili; Zhang, Huagang; Zhang, Xiaoyan; Zhang, Yingshuang; Shui, Wei; Li, Linsong; Fan, Dongsheng; Zhang, Jun^*

来源：Amyotrophic Lateral Sclerosis, 2007, 8(3): 144-149.

DOI：10.1080/17482960601179373

• amyotrophic lateral sclerosis
• age onset
• polymorphisms
• vascular endothelial growth factor

This study investigated the association between polymorphisms in vascular endothelial growth factor (VEGF) gene (-1558C-T, - 190A-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((R)) 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 9.4years 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 27.9(p<0.001) years and 211.7(pv0.001) years for -1154A/G and -1154G/G genotypes, respectively. The VEGF -1558C-T had a positive effect in the -1558C/T group (p50.007, b57.0) and -1558T/ T (pv0.001, b59.6) 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.

• 出版日期2007
• 单位北京大学