Multiple sclerosis risk factors contribute to onset heterogeneity

Briggs, Farren; Yu, Justin C.; Davis, Mary F.; Jiangyang, Jinghong; Fu, Shannon; Parrotta, Erica; Gunzler, Douglas D.; Ontaneda, Daniel

doi:10.1016/j.msard.2018.12.007

Cited by 42 publications

(29 citation statements)

References 32 publications

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“…[47][48][49] The inverse impact of the BMI on physical disability was also recorded in the research of Flauzino et al 50 In several studies as well as in the present one, it was shown that BMI may be considered as a factor that can change during the progression of the disease and that there was an increased incidence of lower values of this parameter with the progression of the disease ie with the transition from RR to SP form. 39 Obesity, among other factors such as gender, age, genetic profile and smoking, has a disease-modifying effect by forming its phenotypic presentation and contributes to the occurrence and progression of MS. 51,52 Research performed at the molecular level showed that high BMI negatively affected the course and form of MS, since the existence of obesity leads to a modulation of the number of monocytes through the ceramide-induced DNA methylation of the antiproliferative genes. 53 MRI studies showed that lifestyle factors, including obesity, influenced the acceleration of cerebral atrophy, and the appearance of new lesions in patients with MS. 54 Prediction of the MS course is nowadays one of the foci of considerable research.…”

Section: Resultsmentioning

confidence: 99%

Association of body mass index with progression and prediction of multiple sclerosis

Tadić¹,

Đajić²,

Grgić³

et al. 2020

Scripta Medica

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Background/Aim: Multiple sclerosis is a disease whose aetiology involves multifactorial interactions among genetic and environmental factors. Obesity is one of the most important environmental factors conducive to the onset and progression of the disease. The aim of the study was to determine the value of body mass index (BMI) in a population of patients with multiple sclerosis compared to the general population, in order to assess the relation between the BMI and physical disability in patients with multiple sclerosis and the influence of the BMI on the course and progression of the disease. Methods: A cross-sectional study was performed in 100 patients suffering from multiple sclerosis (experimental group) and 50 healthy people (control group). In order to determine the degree of physical disability, the Expanded Disability Status Scale (EDSS) was used. Clinical and demographic data and values of the BMI in both studied groups were collected. Statistical analysis included the descriptive statistics, t-test, chi-square test, analysis of variance, correlation and regression analysis. Results: Mean body weight and BMI were significantly higher in the control group (p< 0.05). There was no significant correlation between EDSS and BMI (p = 0.574). There was a correlation between the course of MS and the fact whether BMI was abnormal or normal (p = 0.031). Conclusion: BMI is an environmental factor that significantly correlates with the progression and prediction of multiple sclerosis, but not to the degree of physical disability.

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Section: Resultsmentioning

confidence: 99%

Association of body mass index with progression and prediction of multiple sclerosis

Tadić¹,

Đajić²,

Grgić³

et al. 2020

Scripta Medica

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“…There is a higher clinical concordance rate (25%-30%) among monozygotic or identical twins than dizygotic or fraternal twins (3%-7%) [25]. HLA-DRB1*15:01, genetic risk score (GRS), and smoking were associated with earlier onset of disease [26]. A significant interaction between NAT1 variant rs7388368, HLA-DRB1*15:01, and HLA-A*02 was observed among smokers [23,27].…”

Section: Epigenetics Of Msmentioning

confidence: 99%

Role of Smoking in the Pathogenesis of Multiple Sclerosis: A Review Article

Nishanth

Tariq

Nzvere

et al. 2020

Cureus

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Multiple sclerosis (MS) is a complex and unpredictable neurological condition. It is the most commonly seen autoimmune disorder. The incidence of disease and its prevalence are growing worldwide. Early identification of the disease and accurate diagnosis is important to prevent further complications and disability. The etiology remains unclear, and it is believed that complex gene-environment interactions play an essential role. Genetic predisposition only describes a portion of the disease risk, whereas lifestyle and environmental factors are significant contributors. Smoking was identified as an important risk factor for MS. The main objectives of this review were to examine the underlying mechanisms of immune dysregulation in the development of MS, explore the association between smoking and MS, and identify other genetic and environmental factors that alter the risk of developing the disease. We searched PubMed for articles relevant to the study topic published between 2000 and 2020 using the search terms "multiple sclerosis," "cigarette smoking," "risk factors," and, "epigenetics." Studies reveal a marked association between smoking and the risk of MS. Unlike genetic risk factors, many lifestyles and environmental factors can be adjusted, with potential for prevention, particularly for people at the highest risk, such as families of individuals with MS.

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“…Although HLA-DRB1*15 is a common susceptibility gene for MS in Caucasians and Japanese, the phenotype frequency of DRB1*15:01 ranges between 45% and 60% in European MS patients (10–30% in the general population) but is only approximately 30% in Japanese patients (16–17% in the general population) [ 26 , 27 , 29 , 37 – 39 ]. Conversely, the phenotype frequency of HLA-DRB1*04:05 was reported to be 0.7% in MS patients in Italy [ 37 ], and 0–5.3% in the European general population [ 40 ], but up to 25% in the Japanese general population and around 45% in Japanese MS patients [ 27 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod

Watanabe

Nakamura

Isobe

et al. 2020

J Neuroinflammation

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Background Progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) is a rare but serious complication of some disease-modifying drugs used to treat multiple sclerosis (MS). Japanese MS patients treated with fingolimod were reported to be 10 times more likely to develop PML than equivalent patients in other countries. The strongest susceptibility human leukocyte antigen ( HLA ) class II alleles for MS are distinct between races ( DRB1*15:01 for Caucasians and DRB1*04:05 and DRB1*15:01 for Japanese); therefore, we investigated whether HLA class II alleles modulate anti-JCV antibody serostatus in Japanese MS patients with and without fingolimod. Methods We enrolled 128 Japanese patients with MS, in whom 64 (50%) were under fingolimod treatment at sampling, and examined the relationship between HLA class II alleles and anti-JCV antibody serostatus. Serum anti-JCV antibody positivity and index were measured using a second-generation two-step assay and HLA-DRB1 and -DPB1 alleles were genotyped. Results HLA-DRB1*15 carriers had a lower frequency of anti-JCV antibody positivity (57% vs 78%, p = 0.015), and lower antibody index (median 0.42 vs 1.97, p = 0.037) than non-carriers. Among patients without HLA-DRB1*15 , DRB1*04 carriers had a higher seropositivity rate than non-carriers (84% vs 54%, p = 0.030), and DPB1*04:02 carriers had a higher anti-JCV antibody index than non-carriers (3.20 vs 1.34, p = 0.008) although anti-JCV antibody-positivity rates did not differ. Patients treated with fingolimod had a higher antibody index than other patients (1.46 vs 0.64, p = 0.039) and treatment period had a positive correlation with antibody index ( p = 0.018). Multivariate logistic regression analysis revealed that age was positively associated, and HLA-DRB1*15 was negatively associated with anti-JCV antibody positivity (odds ratio [OR] = 1.06, p = 0.006, and OR = 0.37, p = 0.028, respectively). Excluding HLA-DRB1*15 -carriers, DRB1*04 was an independent risk factor for the presence of anti-JCV antibody (OR = 5.50, p = 0.023). Conclusions HLA-DRB1*15 is associated with low anti-JCV antibody positive rate and low JCV antibody index, and in the absence of DRB1*15 , DRB1*04 carriers are associ...

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Multiple sclerosis risk factors contribute to onset heterogeneity

Cited by 42 publications

References 32 publications

Association of body mass index with progression and prediction of multiple sclerosis

Association of body mass index with progression and prediction of multiple sclerosis

Role of Smoking in the Pathogenesis of Multiple Sclerosis: A Review Article

Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod

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