Smoking and multiple sclerosis susceptibility.
Ontology highlight
ABSTRACT:
SUBMITTER: Hedstrom AK
PROVIDER: S-EPMC3898140 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:To apply quantitative susceptibility mapping (QSM) in the basal ganglia of patients with multiple sclerosis (MS) and relate the findings to R2* mapping with regard to the sensitivity for clinical and morphologic measures of disease severity.The local ethics committee approved this study, and all subjects gave written informed consent. Sixty-eight patients (26 with clinically isolated syndrome, 42 with relapsing-remitting MS) and 23 control subjects underwent 3-T magnetic resonance (MR) imaging. Susceptibility and R2* maps were reconstructed from the same three-dimensional multiecho spoiled gradient-echo sequence. Mean susceptibilities and R2* rates were measured in the basal ganglia and were compared between different phenotypes of the disease (clinically isolated syndrome, MS) and the control subjects by using analysis of variance, and regressing analysis was used to identify independent predictors.Compared with control subjects, patients with MS and clinically isolated syndrome had increased (more paramagnetic) magnetic susceptibilities in the basal ganglia. R2* mapping proved less sensitive than QSM regarding group differences. The strongest predictor of magnetic susceptibility was age. Susceptibilities were higher with increasing neurologic deficits (r = 0.34, P < .01) and lower with normalized volumes of gray matter (r = -0.35, P < .005) and the cortex (r = -0.35, P < .005).QSM provides superior sensitivity over R2* mapping in the detection of MS-related tissue changes in the basal ganglia. With QSM but not with R2* mapping, changes were already observed in patients with clinically isolated syndrome, which suggests that QSM can serve as a sensitive measure at the earliest stage of the disease.
| S-EPMC3632806 | biostudies-other
Project description:Tobacco smoke is an important modifiable environmental risk factor for multiple sclerosis (MS) risk. The population attributable fraction (AF) of MS due to smoking can be used to assess the contribution of smoking to the risk of MS development. We conducted a matched case-control study, including individuals with MS and population-based controls. Overall, sex- and genetic risk score-stratified AF due to smoking were calculated by fitting logistic regression models. We included 9,419 individuals with MS and 9,419 population-based matched controls. At the time of MS onset 44.1% of persons with MS and 35.9% of controls ever regularly smoked of which 38.1% and 29.2% were still smoking. The overall AF was 13.1% (95%CI: 10.7 to 15.4). The AF was 10.6% (95%CI: 7.4 to 13.7) in females and 19.1% (95%CI: 13.1 to 25.1) in males. The AF was 0.6% (95%CI: 0.0 to 2) in ex-smokers. In those having human leucocyte antigen (HLA) and non-HLA risk scores above the median levels of controls, the AF was 11.4% (95%CI: 6.8 to 15.9) and 12% (95%CI: 7.7 to 16.3), respectively. The AF was 17.6% (95%CI: 10.2 to 24.9) and 18.6% (95%CI: 5.5 to 31.6) in those with HLA and non-HLA risk scores below the median levels in controls, respectively. We noticed a decline in AF in recent birth cohorts. This study indicates that at least 13% of cases of MS could be prevented through the avoidance of tobacco smoking. Considering the prevalence of MS, this represents a very large group of people in absolute number.
| S-EPMC8927036 | biostudies-literature
Project description:BackgroundMultiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then.Methods/principal findingsWe performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35-1.63, p < 10⁻¹⁵; non-conservative: RR 1.52, 95% CI 1.39-1.66, p < 10⁻¹⁹). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98-3.61, p = 0.06).DiscussionOur results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors.
| S-EPMC3020969 | biostudies-literature
Project description:Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.
| S-EPMC2880217 | biostudies-literature
Project description:BackgroundStriking changes in the demographic pattern of multiple sclerosis (MS) strongly indicate an influence of modifiable exposures, which lend themselves well to intervention. It is important to pinpoint which of the many environmental, lifestyle, and sociodemographic changes that have occurred over the past decades, such as higher smoking and obesity rates, are responsible. Mendelian randomization (MR) is an elegant tool to overcome limitations inherent to observational studies and leverage human genetics to inform prevention strategies in MS.MethodsWe use genetic variants from the largest genome-wide association study for smoking phenotypes (initiation: N = 378, heaviness: N = 55, lifetime smoking: N = 126) and body mass index (BMI, N = 656) and apply these as instrumental variables in a two-sample MR analysis to the most recent meta-analysis for MS. We adjust for the genetic correlation between smoking and BMI in a multivariable MR.ResultsIn univariable and multivariable MR, smoking does not have an effect on MS risk nor explains part of the association between BMI and MS risk. In contrast, in both analyses each standard deviation increase in BMI, corresponding to roughly 5 kg/m2 units, confers a 30% increase in MS risk.ConclusionDespite observational studies repeatedly reporting an association between smoking and increased risk for MS, MR analyses on smoking phenotypes and MS risk could not confirm a causal relationship. This is in contrast with BMI, where observational studies and MR agree on a causal contribution. The reasons for the discrepancy between observational studies and our MR study concerning smoking and MS require further investigation.
| S-EPMC7501136 | biostudies-literature
Project description:ObjectiveTo explore the nature of genetic-susceptibility to multiple sclerosis (MS) in African-Americans.BackgroundRecently, the number of genetic-associations with MS has exploded although the MS-associations of specific haplotypes within the major histocompatibility complex (MHC) have been known for decades. For example, the haplotypes HLA-DRB1*15:01~HLA-DQB1*06:02, and HLA-DRB1*03:01~ HLA-DQB1*02:01 have odds ratios (ORs) for an MS-association orders of magnitude stronger than many of these newly-discovered associations. Nevertheless, all these haplotypes are part of much larger conserved extended haplotypes (CEHs), which span both the Class I and Class II MHC regions. African-Americans are at greater risk of developing MS compared to a native Africans but at lesser risk compared to Europeans. It is the purpose of this manuscript to explore the relationship between MS-susceptibility and the CEH make-up of our African-American cohort.Design/methodsThe African-American (AA) cohort consisted of 1,305 patients with MS and 1,155 controls, who self-identified as being African-American. For comparison, we used the 18,492 controls and 11,144 MS-cases from the predominantly European Wellcome Trust Case Control Consortium (WTCCC) and the 28,557 phased native Africans from the multinational "Be the Match" registry. The WTCCC and the African-Americans were phased at each of five HLA loci (HLA-A, HLA-C, HLA-B, HLA-DRB1 and HLA-DQB1) and the at 11 SNPs (10 of which were in non-coding regions) surrounding the Class II region of the DRB1 gene using previously-published probabilistic phasing algorithms.ResultsOf the 32 most frequent CEHs, 18 (56%) occurred either more frequently or exclusively in Africans) whereas 9 (28%) occurred more frequently or exclusively in Europeans. The remaining 5 CEHs occurred in neither control group although, likely, these were African in origin. Eight of these CEHs carried the DRB1*15:03~DQB1*06:02~a36 haplotype and three carried the DRB1*15:01~DQB1*06:02~a1 haplotype. In African Americans, a single-copy of the European CEH (03:01_07:02_07:02_15:01_06:02_a1) was associated with considerable MS-risk (OR = 3.30; p = 0.0001)-similar to that observed in the WTCCC (OR = 3.25; p<10-168). By contrast, the MS-risk for the European CEH (02:01_07:02_07:02_15:01_06:02_a1) was less (OR = 1.49; ns)-again, similar to the WTCCC (OR = 2.2; p<10-38). Moreover, four African haplotypes were "protective" relative to a neutral reference, to three European CEHs, and also to the five other African CEHs.ConclusionsThe common CEHs in African Americans are divisible into those that are either African or European in origin, which are derived without modification from their source population. European CEHs, linked to MS-risk, in general, had similar impacts in African-Americans as they did in Europeans. By contrast, African CEHs had mixed MS-risks. For a few, the MS-risk exceeded that in a neutral-reference group whereas, for many others, these CEHs were "protective"-perhaps providing a partial rationale for the lower MS-risk in African-Americans compared to European-Americans.
| S-EPMC8352072 | biostudies-literature
Project description:It is unclear whether smoking interacts with different aspects of Epstein-Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case-control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p?<?0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2-0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI - 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004-0.4), but not between past smoking and IM history (AP - 0.06, 95% CI - 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved.
| S-EPMC7335184 | biostudies-literature
Project description:The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys [median (IQR) 5.03 (3.71, 6.34)], MSWS-12 [median (IQR) 5.28 (3.62, 6.94)] and HADS-Depression [median (IQR) 0.71 (0.47, 0.96)] scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores [median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively] while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis.
| S-EPMC9128822 | biostudies-literature
Project description:The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p?=?9.8×10(-4), OR?=?1.34; rs4872077, in TRAILR-1 gene, p?=?0.005, OR?=?1.72; and rs1001793 in TRAILR-2 gene, p?=?0.012, OR?=?0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p?=?2.12×10(-5), OR?=?0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS.
| S-EPMC3140982 | biostudies-literature
Project description:BackgroundThe incidence of multiple sclerosis (MS) is rising in women.ObjectiveTo determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content.MethodsWe conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record.ResultsWe identified 400 women with incident MS/CIS and 3904 matched controls. Forty- percent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21-1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29-2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95).ConclusionsOur findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.
| S-EPMC4780760 | biostudies-literature