Polymorphisms of apolipoprotein E and Japanese patients with multiple sclerosis

The relation between apolipoprotein (A PO E) gene polymorphisms and disease progression of multiple sclerosis (MS) is controversial. The present study was designed to investigate the relation between A PO E gene polymorphisms and Japanese patients with MS. We analysed the frequencies of A PO E gene polymorphisms in 135 MS patients and 134 healthy controls, using PC R-RFLP. The results showed no significant differences in the distribution of A PO E gene polymorphisms between MS patients and controls. With regard to disease progression, there was no association between A PO E gene polymorphisms and ε4 allele positivity and disease progression index (EDSS/years). Furthermore, in patients with more than 10 years of disease onset, there were no significant differences between the frequencies of ε4 allele and patients with EDSS of more than 6. A lthough the low rate of ε4 allele in Japan should be taken into consideration, our results showed no relation between APO E gene polymorphisms and Japanese patients with MS.

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An examination of the association between b2 adrenergic receptor polymorphisms and multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458502ms848oa ◽

2002 ◽

Vol 8 (6) ◽

pp. 475-478 ◽

Cited By ~ 6

Author(s):

M Niino ◽

S Kikuchi ◽

R Miyagishi ◽

T Fukazawa ◽

I Yabe ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adrenergic Receptor ◽

Gene Polymorphisms ◽

Clinical Characteristics ◽

Mononuclear Cells ◽

Disease Onset ◽

Japanese Patients ◽

Peripheral Blood Mononuclear ◽

Altered Expression ◽

Control Subjects

In multiple sclerosis (MS), β-adrenergic receptor densities on peripheral blood mononuclear cells are enhanced, while the astrocytes present in plaques lack β2 adrenergic receptor (β2AR) expression. This differentially altered expression suggests that β2ARs may influence the pathogenesis of MS. In the present study, we investigated the association of polymorphisms of the β2AR gene with the occurrence of MS. Our results showed no significant differences in the distribution of the polymorphisms between MS patients overall and control subjects. Furthermore, no association was observed between the presence of β2AR gene polymorphisms and clinical characteristics, such as age at disease onset and disease severity. While a trend towards an increase of the Gly allele frequency in codon 16 was observed in the secondary-progressive MS, this result was not significantly different from that observed in relapsing-remitting MS patients or control subjects. Together, our findings suggest that the presence of β2AR gene polymorphisms may be inconclusive in the susceptibility to MS or in the clinical characteristics of Japanese patients with MS and, therefore, need further studies.

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An assessment of the association between IL-2 gene polymorphisms and Japanese patients with multiple sclerosis

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(02)00307-6 ◽

2002 ◽

Vol 205 (1) ◽

pp. 47-50 ◽

Cited By ~ 11

Author(s):

Seiji Kikuchi ◽

Masaaki Niino ◽

Toshiyuki Fukazawa ◽

Ichiro Yabe ◽

Kunio Tashiro

Keyword(s):

Multiple Sclerosis ◽

Gene Polymorphisms ◽

Japanese Patients

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Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/000456303766477020 ◽

2003 ◽

Vol 40 (4) ◽

pp. 382-387 ◽

Cited By ~ 15

Author(s):

Prabhat Kumar ◽

Kalpana Luthra ◽

Manjari Dwivedi ◽

Vinay K Behl ◽

Ravinder M. Pandey ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Gene Polymorphisms ◽

Asian Indians ◽

E Gene ◽

Apo E ◽

Premature Myocardial Infarction ◽

E4 Allele ◽

Conventional Risk Factors

Objectives: Several factors, including abdominal obesity, insulin resistance, diabetes mellitus and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of apolipoprotein E (apo E) gene polymorphisms in premature myocardial infarction (MI) in this population. This study aimed to study the role of apo E gene polymorphisms in premature MI patients and their relation to serum lipid levels. Design and methods: Apo E gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors. Results: Higher frequencies of the apo E4 allele (P<0·0001) and of genotypes E3/E4 (P<0·005) and E4/E4 (P<0·005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45·7 (4·9-421·3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8·7 (0·9-86·6)] and those with a high waist : hip ratio [OR (95% CI): 5·6 (1·4-21·2)]. Conclusion: Based on the robust association, the apo E4 allele should be considered as an independent risk factor for premature MI in Asian Indians.

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Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis

Journal of Central Nervous System Disease ◽

10.1177/11795735211050712 ◽

2021 ◽

Vol 13 ◽

pp. 117957352110507

Author(s):

Qi Wu ◽

Qin Wang ◽

Jennifer Yang ◽

Jacob WS Martens ◽

Elizabeth A Mills ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Progression ◽

Plasma Levels ◽

Disease Onset ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

Background: The long-term prognosis of relapsing-remitting multiple sclerosis (RRMS) is usually unfavorable as most patients transition to secondary progressive multiple sclerosis (SPMS) with accumulative disability. A rare form of non-progressive multiple sclerosis (MS) also exists, known as benign MS (BMS or NPMS), which lacks disease progression defined as Expanded Disability Status Scale (EDSS) ≤3 after 15 years of disease onset without treatment. Purpose: Our study aims to identify soluble plasma factors predicting disease progression in multiple sclerosis (MS). Research Design and Study Sample: We utilized Luminex multiplex to analyze plasma levels of 33 soluble factors, comparing 32 SPMS patients to age-, sex-, and disease duration-matched non-progressive BMS patients, as well as to RRMS patients and healthy controls. Results: Plasma levels of EGF, sCD40L, MCP1/CCL2, fractalkine/CX3CL1, IL-13, Eotaxin, TNFβ/LTα, and IL-12p40 were significantly different between the various types of MS. Plasma sCD40L was significantly elevated in SPMS compared to BMS and RRMS. The combination of MCP1/CCL2 and sCD40L discriminated between RRMS and SPMS. MCP1/CCL2 was found to be the most effective classifier between BMS and RRMS, while BMS was most effectively distinguished from SPMS by the combination of sCD40L and IFNγ levels. Conclusions: These differences may facilitate personalized precision medicine and aid in the discovery of new therapeutic targets for disease progression through the improvement of patient stratification.

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Association of the Angiotensinogen M235T and APO E Gene Polymorphisms in Turkish Type 2 Diabetic Patients with and without Nephropathy

Renal Failure ◽

10.3109/0886022x.2011.568133 ◽

2011 ◽

Vol 33 (5) ◽

pp. 469-474 ◽

Cited By ~ 8

Author(s):

Kadriye Altok Reis ◽

Fatma Ayerden Ebinç ◽

Eyüp Koç ◽

Hüseyin Demirci ◽

Yasemin Erten ◽

...

Keyword(s):

Gene Polymorphisms ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

E Gene ◽

Apo E ◽

Type 2 Diabetic

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Cognitive impairment in patients with multiple sclerosis: association with the APOE gene and promoter polymorphisms

Multiple Sclerosis Journal ◽

10.1177/1352458506070682 ◽

2007 ◽

Vol 13 (1) ◽

pp. 25-32 ◽

Cited By ~ 22

Author(s):

B A Parmenter ◽

D R Denney ◽

S G Lynch ◽

L S Middleton ◽

L M Harlan

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Physical Disability ◽

Neuropsychological Test ◽

Disease Onset ◽

Apoe Gene ◽

Promoter Polymorphisms ◽

Severe Cognitive Impairment ◽

Ε4 Allele ◽

Male Patients

Background Studies examining the ε4 allele of the APOE gene as a factor affecting the severity of multiple sclerosis (MS) have yielded conflicting results. The focus of these studies on physical disability to the neglect of cognitive impairment is surprising in light of the associations between the ε4 allele and other dementia conditions. Only two studies examine the relationship between the ε4 allele and cognitive impairment. Methods A neuropsychological test battery was administered to 263 MS patients, and their current disability status was evaluated. Genotypes were determined for APOE epsilon and for two promoter region polymorphisms (-219 G/T and -491 A/T). Results Although effects were generally weak, female patients with the -491 AA genotype had a later age of disease onset, lower disability scores, and somewhat higher scores on the cognitive battery. Male patients with the ε2 allele had lower disability and higher scores on the cognitive battery. The ε4 allele was not related to physical disability, and there was no difference between ε4+and ε4– patients in overall cognitive performance. However, when patients with severe cognitive impairment were identified, a greater proportion (52%) of these patients had the ε4 allele than those in the unimpaired group (27%). Conclusion An association with the ε4 allele was evident in this study, but only in cases of severe cognitive impairment.

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Functional Gene Polymorphisms of Interleukin-10 are Associated with Liver Disease Progression in Japanese Patients with Hepatitis C Virus Infection

Internal Medicine ◽

10.2169/internalmedicine.50.4581 ◽

2011 ◽

Vol 50 (7) ◽

pp. 659-666 ◽

Cited By ~ 10

Author(s):

Chihiro Ishida ◽

Yuichiro Ikebuchi ◽

Kinya Okamoto ◽

Yoshikazu Murawaki

Keyword(s):

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Virus Infection ◽

Disease Progression ◽

Gene Polymorphisms ◽

Japanese Patients ◽

Interleukin 10 ◽

Hepatitis C Virus Infection ◽

Liver Disease Progression

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Timing of birth and disease progression in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458508090662 ◽

2008 ◽

Vol 14 (6) ◽

pp. 793-798 ◽

Cited By ~ 9

Author(s):

M Koch ◽

J De Keyser ◽

H Tremlett

Keyword(s):

Multiple Sclerosis ◽

Natural History ◽

Disease Progression ◽

Disease Onset ◽

Later Life ◽

Season Of Birth ◽

Month Of Birth ◽

Birth Month ◽

Kaplan Meier ◽

Younger Age

Background The timing of birth has recently been associated with the risk of developing multiple sclerosis (MS) in later life. Whether the timing of birth also influences the disease course of MS is unknown. Objective To investigate whether the season or month of birth influences the timing of secondary progression or the time to landmark disability outcomes in MS. Methods To allow confirmation of findings, all analyses were performed in duplicate in two large natural history cohorts from geographically distinct but seasonally similar locations in Europe and North America. Kaplan–Meier survival analyses were used to investigate the influence of month and season of birth on 1) the time to and age at the development of secondary progression in patients with a relapsing disease onset and 2) the time to reach an Expanded Disability Status Scale (EDSS) score of 6.0 in patients with primary progressive and relapsing MS. Results No association between the month or season of birth and disease progression could be found, which was reproducible in both natural history cohorts. A seasonal trend was observed for the time to and age at secondary progression in Groningen, with March babies exhibiting a shorter time to and younger age at secondary progression. The birth month affected time to EDSS 6 for those with relapsing MS in British Columbia, with January babies exhibiting a longer time to EDSS 6. Neither finding could be reciprocated in the other natural history cohort. Conclusion The season or month of birth does not appear to influence disease progression of MS.

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Elucidation of predictors of disease progression in patients with relapsing polychondritis at the onset: potential impact on patient monitoring

BMC Rheumatology ◽

10.1186/s41927-020-00141-8 ◽

2020 ◽

Vol 4 (1) ◽

Author(s):

Jun Shimizu ◽

Yoshihisa Yamano ◽

Kimito Kawahata ◽

Noboru Suzuki

Keyword(s):

Mortality Rate ◽

Disease Progression ◽

Disease Onset ◽

Relapsing Polychondritis ◽

Japanese Patients ◽

Nonparametric Tests ◽

Organ Involvement ◽

Onset Potential ◽

Respiratory Involvement

Abstract Background In patients with relapsing polychondritis (RP), organ involvement developed in those with progressive and/or long disease courses. For their management, elucidation of a subgroup suggesting disease progression is awaited. Methods We previously conducted a physician’s questionnaire-based retrospective study to elucidate major clinical features of Japanese patients with RP. We here evaluated organ involvement at disease onset and at the last follow-up. We then counted cumulative numbers of involved organs at the last follow-up in 229 RP patients and compared them with involved organ numbers at disease onset, as possible indicators of disease progression. We assigned their prognosis at the last follow-up into “patient prognostic stages” from no medication (stage 1) to death (stage 5). We utilized nonparametric tests for group comparisons. Results Involved organ numbers per-patient were 1.13 ± 0.03 at disease onset and 3.25 ± 0.10 at the last follow-up (disease duration was 4.69 ± 0.33 years), and increased along with the patient prognostic stages. At disease onset, 135 and 48 patients had auricular involvement (59% of 229 patients, defined as auricular-onset subgroup; AO) and respiratory involvement (21%, respiratory-onset subgroup; RO), respectively. 46 patients presented with other conditions (20%, miscellaneous-onset subgroup; MO) including CNS, ocular, and inner ear involvement, among others. RO patients showed worse (poorer) prognostic stages than AO patients. MO patients developed respiratory and/or auricular involvement thereafter and then showed significantly higher mortality rate (15%; 7/46) than AO patients (5.9%; 8/135). In RP patients who did not develop respiratory involvement until the last follow-up (throughout the disease course; 117 patients), mortality rate was 19% in 26 MO patients and 3.3% in 91 AO patients. Accordingly, RO patients and MO patients associated with relatively poor prognosis compared with AO patients. Conclusions Allocation of patients to RO and MO subgroups was suggested to associate with poorer prognosis of RP than AO subgroups, especially AO subgroups without respiratory involvement throughout. All RP patients deserve careful monitoring but special attention should be paid to MO patients because of their diverse and accelerated disease progression.

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