Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The ...aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D 25(OH) vitamin D levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p=0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p=0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p=0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p=0.65). In subanalysis, patients with GA+AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p=0.03). No increased risk was observed in GT+TT genotypes of CYP27B1 rs10877012 (p=0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA+AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.
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•The usage of Melatonin increases the levels of BMAL1 clock gene in Parkinson`s disease patients.•High-dose of Melatonin failed to decrease the presence of insomnia.•Melatonin could ...reduce motor symptoms in OFF Parkinson´s disease.
Sleep disorders are a widespread condition in patients with Parkinson's disease (PD), which has been linked to a deregulation of the circadian cycle and therefore of the clock genes. The aim of this study was to evaluate the effect of melatonin (MEL) on the PER1 and BMAL1 clock genes in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial pilot study was conducted in 26 patients with stage 1–3 PD according to the Hoehn & Yahr scale, who received either 25 mg of MEL or a placebo at noon and 30 min before bedtime for three months. The relative expression of the PER1 and BMAL1 genes was measured, as well as the presence of daytime, nocturnal, and global sleepiness, and the progression of PD. The levels of the PER1 and BMAL1 genes at baseline were 0.9 (0.1–3) vs. 0.56 (0.1−2.5), respectively; while after the intervention with MEL or placebo the BMAL1 levels increased to 2.5 (0−3.70) vs. 2.2 (0.10–3.30), respectively (d = 0.387). Fifty percent (50 %) of patients had daytime sleepiness and sixty-five percent (65 %) had abnormal nighttime sleepiness, yet neither group showed changes after the intervention. Patients with PD exhibited an alteration in the levels of the clock genes: MEL increased the levels of BMAL1, but the PER1 levels remained unchanged.
A very high prevalence of multiple sclerosis (MS) has been reported in some Western European and North American countries. The few surveys of MS epidemiology in South America reveal lower prevalence ...rates, implying that susceptibility varies between distinct ethnic groups, thus forming an important determinant of the geographic distribution of the disease. The objective of this study is to review MS prevalence estimates in different Latin American and Caribbean countries. We reviewed surveys of regional MS prevalence from 1991 to 2011. Sources included an online database, authors’ reports and proceedings or specific lectures from regional conferences. We obtained a total of 30 prevalence surveys from 15 countries, showing low/medium MS prevalence rates. Both the number and the quality of prevalence surveys have greatly improved in this region over recent decades. This is the first collaborative study to map the regional frequency of MS. Establishment of standardized methods and joint epidemiological studies will advance future MS research in Latin America and the Caribbean.
Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote ...tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFα levels; secondary outcomes were IL-1β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P≤0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found. Conclusion. Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS.
Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic ...arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.
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•MIF is a cytokine associated with tissue damage in multiple autoimmune diseases•5,7 heterozygous genotype contribute to the increase of severity and damage progression in MS•Polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers in the MS severity and progression in male
Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD).
To investigate these observations by the study of persons at ...risk for autosomal dominant forms of AD.
Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE epsilon4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs.
MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE epsilon4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores.
This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE epsilon4 allele did not demonstrate large influences on neuropsychological performance.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has ...neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS).
To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement.
Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified.
In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized.
The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS.
The
HLA-DRB1*15:01
allele has a demonstrated risk for the development of multiple sclerosis (MS) in most populations around the world. The single nucleotide polymorphism (SNP) rs3129934 is found in ...linkage disequilibrium with the risk haplotype formed by the
HLA-DRB1*15:01
and
HLA-DQB1*06:02
alleles, and it is considered a reliable marker of the presence of this haplotype. Native Americans have a null or low prevalence of MS. In this study, we sought to identify the frequency of rs3129934 in the
Wixárika
ethnic group as well as in Mestizo (mixed race) patients with MS and in controls from western Mexico. Through real-time polymerase chain reaction (PCR) using TaqMan probes, we analyzed the allele and genotype frequencies of rs3129934 in Mestizo individuals with and without MS and in 73
Wixárika
subjects from the state of Jalisco, Mexico. The
Wixárika
subjects were homozygote for the C allele of rs3129934. The allele and genotype frequency in Mestizos with MS was similar to that of other MS populations with Caucasian ancestry. The absence of the T risk allele rs3129934 (associated with the haplotype
HLA-DRB1*15:01
,
HLA-DQ1*06:02
) in this sample of
Wixárika
subjects is consistent with the unreported MS in this Amerindian group, related to absence of such paramount genetic risk factor.
Prior functional magnetic resonance imaging (fMRI) studies have found increased activity-related blood oxygen level-dependent (BOLD) signal in cognitively normal persons at genetic risk for ...Alzheimer's disease (AD). This has been interpreted as a compensatory response to incipient AD pathology. We studied the effects of fully penetrant familial Alzheimer's disease (FAD) mutations and apolipoprotein E (APOE) genotype on BOLD fMRI during a novelty encoding task in presymptomatic subjects. Twenty-three Mexican or Mexican-American persons at-risk for inheriting FAD mutations performed a block design novelty encoding task, and activation exhibited by FAD mutation carriers (MCs) was contrasted with that of noncarriers (NCs) and among APOE genotype groups. FAD MCs (n = 14) showed decreased BOLD activation in the anterior cingulate gyrus relative to 9 NCs. No increased activation was seen in MCs relative to NCs. Four APOE ε3/4 carriers demonstrated increased BOLD signal compared with 14 ε3/3 carriers in the occipital and perisylvian cortices bilaterally. There were no areas where ε3/3 carriers activated more than ε3/4 carriers. Our findings of increased fMRI activation associated with APOE genotype but not with FAD mutations suggest that APOE exerts an effect on the BOLD signal that is not readily explained as a compensatory phenomenon.