Association of
            <i>APOE</i>
            polymorphisms with disease severity in MS is limited to women

Kantarci, Orhun H.; Hebrink, David D.; Achenbach, Sara J.; Pittock, S J; Altıntaş, Ayşe; Schaefer-Klein, Janet; Atkinson, Elizabeth J.; Andrade, Marisa De; McMurray, Cynthia T.; Rodríguez, Marta; Weinshenker, Brian G.

doi:10.1212/01.wnl.0000113721.83287.83

Cited by 71 publications

(51 citation statements)

References 17 publications

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“…An increasing number of reports have pointed to sex-specific association of common gene polymorphisms with autoimmunity. For instance, CD95 was found to be associated with susceptibility to MS in women (Kantarci et al, 2004a), APOE with disease severity of MS in women (Kantarci et al, 2004b), IFNG with susceptibility to MS in men (Goris et al, 2002;Kantarci et al, 2005) and IL26 with susceptibility to RA in women (Vandenbroeck et al, 2003). These data call for a systematic whole-genome scrutiny for gender-specific autoimmune susceptibility factors.…”

Section: Discussionmentioning

confidence: 96%

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Suppiah

Rooney

Vandenbroeck

2006

Experimental and Molecular Pathology

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Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. Suppiah, V., Rooney, M., & Vandenbroeck, K. (2006). Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. AbstractRheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.

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Section: Discussionmentioning

confidence: 96%

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Suppiah

Rooney

Vandenbroeck

2006

Experimental and Molecular Pathology

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“…However, an influence of this isoform on the clinical course of the disease is not established and the interaction with potential confounders should be considered. For example, it was suggested that an influence of apoE polymorphism on the clinical course, and even the risk of MS, could particularly exist in women [23]. Our group has provided evidence for an influence of cigarette smoking in apoE4-carriers, in modulating the clinical severity of RR-MS patients [24].…”

Section: Multiple Sclerosismentioning

confidence: 57%

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Sena¹,

Capela²,

Nóbrega³

et al. 2012

Lipoproteins - Role in Health and Diseases

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“…The authors did not use the MSSS as a measure of disease severity. A previous study 14 suggested that an APOE association with MS severity may be limited to female patients. Although the MK-QTDT test statistic was larger when only MSSS data from female patients in the combined data set were analyzed (T ¼ 2.35, P ¼ 0.02), compared to an analysis of only male patients (T ¼ 1.83, P ¼ 0.07), the same allele at rs394221 was associated with a higher average severity in both groups, and the numeric difference is likely due to the larger sample size of female patients.…”

Section: Discussionmentioning

confidence: 95%

“…[7][8][9][10][11][12][13][14][15] Specifically, the APOE-4 allele was associated with a more severe disease course, whereas carriers of the APOE-2 allele appeared more likely to have a milder form of MS. However, a similar number of studies failed to replicate this association.…”

Section: Introductionmentioning

confidence: 95%

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis

et al. 2006

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Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/ disequilibrium test to a recently proposed MS severity score, the only statistically significant (P ¼ 0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene (PVRL2). Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.

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Association of APOE polymorphisms with disease severity in MS is limited to women

Cited by 71 publications

References 17 publications

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis

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