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- Lambrechts, Diether, et al.
(författare)
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Meta-analysis of VEGF variations in ALS : increased susceptibility in male carriers of the -2578AA genotype
- 2008
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Ingår i: Journal of Medical Genetics. - London : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 46:12, s. 840-846
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted delivery of the angiogenic factor, vascular endothelial growth factor (VEGF), to motor neurons prolongs survival in rodent models of amyotrophic lateral sclerosis (ALS), while mice expressing reduced VEGF concentrations develop motor neuron degeneration reminiscent of ALS, raising the question whether VEGF contributes to the pathogenesis of ALS. An initial association study reported that VEGF haplotypes conferred increased susceptibility to ALS in humans, but later studies challenged this initial finding. Methods and findings: A meta-analysis was undertaken to critically reappraise whether any of the three common VEGF gene variations (−2578C/A, −1154G/A and −634G/C) increase the risk of ALS. Over 7000 subjects from eight European and three American populations were included in the analysis. Pooled odds ratios were calculated using fixed-effects and random-effects models, and four potential sources of heterogeneity (location of disease onset, gender, age at disease onset and disease duration) were assessed. After correction, none of the genotypes or haplotypes was significantly associated with ALS. Subgroup analysis by gender revealed, however, that the −2578AA genotype, which lowers VEGF expression, increased the risk of ALS in males (OR = 1.46 males vs females; 95% CI = 1.19 to 1.80; p = 7.8 10E-5), even after correction for publication bias and multiple testing. Conclusions: This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF −2578AA genotype with increased susceptibility to ALS in males reappraises the link between reduced VEGF concentrations and ALS, as originally revealed by the fortuitous mouse genetic studies.
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| 2. |
- van de Giessen, Elsmarieke, et al.
(författare)
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Association study on glutathione S-transferase omega 1 and 2 and familial ALS
- 2008
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Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa UK Limited. - 1466-0822 .- 1743-4483. ; 9:2, s. 81-84
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione S-transferase omega 1 and 2 (GSTO1 and 2) protect from oxidative stress, a possible pathogenic mechanism underlying the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Significant association of age of onset in Alzheimer's patients with GSTO1 and 2 had recently been identified, suggesting a possibly similar association with ALS. In this study 12 Hapmap tagged SNPs in GSTO1 and 2 were genotyped in 251 Caucasian British, Australian and Swedish familial ALS (FALS) cases. No association was found for age of onset and survival of FALS in the British and Australian patients. In the Swedish patients, association for age of onset was found with several SNPs (p = 0.003-0.048). These results suggest a possible effect of the GSTO1 and 2 locus on age of onset of FALS.
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