Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate

Høgh, Peter; Oturai, A.; Schreiber, K.; Blinkenberg, M.; Jørgensen, Ole Steen; Ryder, L.; Paulson, Olaf B.; Sørensen, P.S.; Knudsen, Gitte M.

doi:10.1191/135245800678827851

Cited by 56 publications

(54 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…functional polymorphism of the apoe gene would then be expected to affect the long-term outcome. the presence of the apoe * ε4 allele or rather of the ε3/ε4 genotype (the ε4/ε4 genotype is rare) has been suggested as an unfavorable prognostic factor independent of age of onset, gender and duration of disease in different studies (77)(78)(79)(80)(81)(82)(83). However, other studies have not confirmed these findings (84)(85)(86).…”

Section: Apolipoprotein E Gene (Apoe)mentioning

confidence: 38%

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

Kallaur

Kaimen-Maciel²,

Morimoto³

et al. 2011

Int J Mol Med

View full text Add to dashboard Cite

Abstract. multiple sclerosis (mS) is an autoimmune disease characterized by areas of inflammation, demyelination and axonal damage. the etiology of mS is multifactorial with an interaction between genetic, environmental and geographical factors. the objective of this study was to review the physiopathology and the genetic polymorphisms associated with the development and clinical course of mS. Studies carried out in populations worldwide showed that polymorphisms in the genes of the major histocompatibility complex (mHc) class ii and class iii have been associated with susceptibility, resistance and clinical forms of mS. considerable attention has been focused on studies evaluating disease-modifying effects in MS that identified seven genes of probable importance such as the Hla class ii, apoe, il-1ra, il-1β, tnf-α, tnf-β and ccr5 genes. However, the results described in the literature about genetic biomarkers in mS are not consistent in the worldwide population. the detection of a single nucleotide polymorphism involved in the etiology and physiopathology of MS is very difficult and, it is likely that, several genetic polymorphisms are involved, each with a small contribution to the susceptibility or resistance to mS. taken together the results show the need for continued research in genetically heterogeneous populations to identify new biomarkers associated with mS that could be used as prognostic markers or as therapeutic targets to modulate the autoimmune response in mS patients. this information may contribute to a better understanding of the physiopathology and treatment of mS, with the possibility of developing different therapeutic strategies according to the genetic profile of each individual.

show abstract

Section: Apolipoprotein E Gene (Apoe)mentioning

confidence: 38%

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

Kallaur

Kaimen-Maciel²,

Morimoto³

et al. 2011

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…In a study in which the frequency of APOE ε4/ε4 homozygotes was significantly higher among MS patients as compared to controls, the APOE ε4/ε4 genotype was associated with increased risk of developing MS (30). The APOE gene consists of multiple alleles, leading to the occurrence of the three common apoE isoforms.…”

Section: Discussionmentioning

confidence: 98%

Multipl Skleroz ile Apolipoprotein E Genetik Polimorfizmi Arasındaki İlişki

Taşdemir¹,

Tamam²,

Yalman³

2013

npa

View full text Add to dashboard Cite

Re cei ved/Ge liş ta ri hi: 21.07.2011 Ac cep ted/Ka bul ta ri hi: 07.05.2012 © Arc hi ves of Neu ropsy chi atry, pub lis hed by Ga le nos Pub lis hing / © Nö rop si ki yat ri Ar şi vi Der gi si, Ga le nos Ya yı ne vi ta ra f›n dan ba s›l m›fl t›r. ABS TRACTBackground: Although the etiology of multiple sclerosis (MS) has not yet been clearly elucidated, MS is a chronic inflammatory disease, in which genetic and environmental factors are involved. The association between apolipoprotein E (APOE) genetic polymorphisms and various neurodegenerative diseases, including MS, is controversial. In the current study, specific APOE genotypes were investigated in patients with MS. Methods: Fifty patients clinically diagnosed with MS and 30 healthy volunteers were included in the study. The APOE genotype was identified via the polymerase chain reaction (PCR) method. The patient and control groups were compared in terms of the frequency of APOE genotypes. Results: The APOE genotype distribution in the patient group was as follows: ε3/ε3, 82.0%; ε3/ε4, 12.0%; and ε2/ε3, 6.0%. There were no significant differences between the patient and control groups with respect to the frequency of APOE genotypes, and APOE ε4 allele carriage (p=0.56). However, the frequency of APOE ε4 allele carriers were significantly higher among male patients (p=0.007). Conclusion: These findings suggest that the APOE genotype has no effect on susceptibility to MS. Further studies with larger sample sizes to be able to include all APOE genotypes are warranted. Identification of genetic factors that may have a role in the etiology of MS will make a substantial contribution to the knowledge of the prevention and treatment of MS. (Arc hi ves of Neu ropsy chi atry 2013; 50: 110-115) Conflict of interest:The authors reported no conflict of interest related to this article. ÖZETAmaç: Multipl skleroz (MS) henüz nedeni çok iyi aydınlatılamamış olmakla birlikte genetik ve çevresel faktörlerin etkisiyle ortaya çıkan kronik inflamatuar bir hastalıktır. MS dahil çeşitli nörodejeneratif hastalıklar ile apolipoprotein E (APOE) genetik polimorfizmi arasındaki ilişki tartışmalıdır. Bu çalışmada MS'li hastalarda belirli APOE genotipleri araştırıldı. Yöntem: Klinik olarak MS tanısı almış 50 hasta ve sağlıklı 30 kişi çalışmaya alındı. APOE genotipi PCR yöntemiyle belirlendi. APOE genotiplerinin hasta ve kontrol grubunda görülme sıklıkları karşılaştırıldı. Bulgular: APOE genotip dağılımı MS grubunda sırayla ε3/ε3 %82,0, ε3/ε4 %12,0, ε2/ε3 %6,0 idi. MS ve kontrol grubu arasında genotiplerin görülme oranlarında belirgin farklılıklar yoktu ve ε4 taşıyıcılığı açısından anlamlı fark saptanmadı (p=0,56). Ancak MS hastalarında erkek cinsiyette ε4 taşıyıcılığı anlamlı olarak yüksek bulundu (p=0,007). Sonuç: Sonuçlarımız APOE genotipinin MS'a yatkınlık üzerinde etkisinin olmadığını düşündürmüştür. Daha fazla olgu ile tüm genotipleri kapsayacak şekilde geniş kapsamlı çalışmalara gerek vardır. Etiyolojide rolü olabilecek genetik faktörlerin aydınlatılması MS hastalığının önlenmesi ve te...

show abstract

“…[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: 97%

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

et al. 2006

View full text Add to dashboard Cite

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.

show abstract

Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate

Cited by 56 publications

References 0 publications

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

Multipl Skleroz ile Apolipoprotein E Genetik Polimorfizmi Arasındaki İlişki

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

Contact Info

Product

Resources

About