No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls

Xuan, Chao; Zhang, Beibei; Li, Ming; Deng, Kaifeng; Yang, Tao; Zhang, Xiange

doi:10.1016/j.jns.2011.05.040

Cited by 23 publications

(18 citation statements)

References 62 publications

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“…In the combined analyses, we had approximately 99% and 72% power to detect an OR of 1.20 at a genome-wide significance threshold (α=5×10 −8 ) for rs429358 and rs7412, respectively. In total, our study exceeded the above mentioned recent meta-analyses6 7 across 58316 and 7706 Caucasian subjects7 by ∼23 900 and 22 000 subjects, respectively.…”

Section: Resultscontrasting

confidence: 41%

“…As a matter of fact, none of the previously performed APOE association studies in MS included more than 450 cases (see supplementary table S1 for an overview of study-specific sample sizes). Even two previous meta-analyses combining published data6 7 were limited in power to detect modest effects (ie, ORs at or below 1.2) at acceptable type-1 error rates, eg, at a genome-wide significance threshold (typically defined as α=5×10 −8 ).…”

Section: Introductionmentioning

confidence: 99%

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Closing the case ofAPOEin multiple sclerosis: no association with disease risk in over 29 000 subjects: Figure 1

et al. 2012

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Section: Resultscontrasting

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Closing the case ofAPOEin multiple sclerosis: no association with disease risk in over 29 000 subjects: Figure 1

et al. 2012

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“…Genotype distributions of controls were used to estimate the frequencies of the putative risk allele (-1858T) using the inverse variance method (Xuan et al, 2011b;Xuan et al, 2012). The deviation from Hardy-Weinberg equilibrium (HWE) for distribution of the allele frequencies was analysed by Fisher's exact test in control groups.…”

Section: Discussionmentioning

confidence: 99%

PTPN22 Gene Polymorphism (C1858T) Is Associated with Susceptibility to Type 1 Diabetes: A Meta‐Analysis of 19,495 Cases and 25,341 Controls

Xuan

Liu

Zhao

et al. 2013

Annals of Human Genetics

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SummaryThe protein tyrosine phosphatase N22 (PTPN22) gene C1858T polymorphism has been reported to be associated with susceptibility to type 1 diabetes (T1D) in relatively small sample sizes. This study aimed at investigating the pooled association by carrying out a meta-analysis on the published studies. The Medline, EBSCO, and BIOSIS databases were searched to identify eligible studies published in English before June 2012. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). The presence of heterogeneity and publication bias was explored by using meta-regression analysis and Begg's test, respectively. A total of 28 studies were involved in this meta-analysis. Across all populations, significant associations were found between the PTPN22 C1858T polymorphism and susceptibility to T1D under genotypic (TT vs. CC [OR = 3.656, 95% CI: 3.139-4.257], CT vs. CC [OR = 1.968, 95% CI: 1.683-2.300]), recessive (OR = 3.147, 95% CI: 2.704-3.663), and dominant models (OR = 1.957, 95% CI: 1.817-2.108). In ethnicityand sex-stratified analyses, similar associations were found among Caucasians and within Caucasian male and female strata. The meta-analysis results suggest that the PTPN22 C1858T polymorphism was associated with susceptibility to T1D among the Caucasian population, and males who carried the -1858T allele were more susceptible to T1D than females.

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“…The ApoE4 allele also increases susceptibility to a more severe MS course (Tamam et al, 2011) leading to an exacerbation of cognitive decline (Shi et al, 2011) and grey matter volume loss (Horáková et al, 2010), which is in line with the ApoE4 allele being a susceptibility factor for Alzheimer's disease, where it interacts with stress to heighten cognitive decline (Sheffler et al, 2014). However, a meta-analysis of ApoE4 on MS susceptibility per se shows no significant effect (Xuan et al, 2011). ApoE4 synergistically interacts with depression, anxiety and stressful life events to increase cognitive decline and dementia susceptibility (Metti et al, 2013;Michels et al, 2012;Comijs et al, 2011;Robertson et al, 2005;.…”

Section: Apoe4 and Melatonin Regulation Of Ms Cognitive Deficitsmentioning

confidence: 99%

Multiple sclerosis: The role of melatonin and N-acetylserotonin

Anderson¹,

Rodriguez

2015

Multiple Sclerosis and Related Disorders

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Multiple sclerosis (MS) is an immune mediated disorder that is under intensive investigation in an attempt to improve on available treatments. Many of the changes occurring in MS, including increased mitochondrial dysfunction, pain reporting and depression may be partly mediated by increased indoleamine 2,3-dioxygenase, which drives tryptophan to the production of neuroregulatory tryptophan catabolites and away from serotonin, N-acetylserotonin and melatonin production. The consequences of decreased melatonin have classically been attributed to circadian changes following its release from the pineal gland. However, recent data shows that melatonin may be produced by all mitochondria containing cells to some degree, including astrocytes and immune cells, thereby providing another important MS treatment target. As well as being a powerful antioxidant, anti-inflammatory and antinociceptive, melatonin improves mitochondrial functioning, partly via increased oxidative phosphorylation. Melatonin also inhibits demyelination and increases remyelination, suggesting that its local regulation in white matter astrocytes by serotonin availability and apolipoprotein E4, among other potential factors, will be important in the etiology, course and treatment of MS. Here we review the role of local melatonin and its precursors, N-acetylserotonin and serotonin, in MS.

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No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls

Cited by 23 publications

References 62 publications

Closing the case ofAPOEin multiple sclerosis: no association with disease risk in over 29 000 subjects: Figure 1

Closing the case ofAPOEin multiple sclerosis: no association with disease risk in over 29 000 subjects: Figure 1

PTPN22 Gene Polymorphism (C1858T) Is Associated with Susceptibility to Type 1 Diabetes: A Meta‐Analysis of 19,495 Cases and 25,341 Controls

Multiple sclerosis: The role of melatonin and N-acetylserotonin

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