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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. |
- Macfarlane, Tatiana V, et al.
(författare)
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Orofacial pain in young adults and associated childhood and adulthood factors: results of the population study, Wales, United Kingdom.
- 2009
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Ingår i: Community dentistry and oral epidemiology. - : Wiley. - 1600-0528 .- 0301-5661. ; 37:5, s. 438-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the study was to investigate the prevalence of orofacial pain (OFP) among young adults (30-31 years old) and to determine the effect of childhood and adulthood risk factors on the occurrence of OFP. METHODS: Prospective cohort study to investigate dental and social effects of malocclusion and effectiveness of orthodontic treatment was conducted in Wales, United Kingdom. At 20-year follow-up 337 subjects aged 30-31 participated (74% from previous follow-up aged 19-20 and 33% from the baseline) and were asked about OFP. RESULTS: The prevalence of OFP was 23% (95% CI: 19%, 28%). Childhood factors, socio-demographic, lifestyle, health behavior factors, history of orthodontic treatment and tooth wear were not associated with OFP. Participants with OFP were more likely to report that their teeth did not fit together properly [odds ratio (OR) = 12.4, 95% CI: 2.7-56.5) and reported previous trauma to the jaws (2.3; 1.3-4.2). Both diurnal and nocturnal teeth clenching and grinding were significantly associated with OFP (3.1; 1.4-7.1). Participants with frequent headaches had increased risk of having OFP (3.7; 1.6-8.4) while having reported 4-10 types of pain in other parts of the body other than the head, was associated with OR = 9.2 (3.7-23.0). An increased tendency to have OFP was seen in those individuals with higher levels of psychological distress (2.3; 1.4-3.9), high score on Life Event Inventory (2.6; 1.3-5.3), depressive symptoms (2.2; 1.2-4.0) and stress (2.2; 1.2-4.0). High self-esteem associated with lower risk of OFP (0.5; 0.3-0.9). CONCLUSIONS: This study shows that OFP is frequently reported by young adults aged 30-31 and supports a multifactorial etiology with factors from many domains, including local mechanical factors, psychological and co-morbidities. However, none of the childhood factors considered in this study were associated with OFP in adulthood.
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