Incident Cases Of Multiple Sclerosis Research Articles

Multiple sclerosis in Canada 2011 to 2031: results of a microsimulation modelling study of epidemiological and economic impacts.

The objective of our study was to present model-based estimates and projections on current and future health and economic impacts of multiple sclerosis (MS) in Canada over a 20-year time horizon (2011-2031). Using Statistics Canada's Population Health Microsimulation Model (POHEM) framework, specifically the population-based longitudinal, microsimulation model named POHEM-Neurological, we identified people with MS from health administrative data sources and derived incidence and mortality rate parameters from a British Columbia population-based cohort for future MS incidence and mortality projections. We also included a utility-based measure (Health Utilities Index Mark 3) reflecting states of functional health to allow projections of health-related quality of life. Finally, we estimated caregiving parameters and health care costs from Canadian national surveys and health administrative data and included them as model parameters to assess the health and economic impact of the neurological conditions. The number of incident MS cases is expected to rise slightly from 4051 cases in 2011 to 4794 cases per 100 000 population in 2031, and the number of Canadians affected by MS will increase from 98 385 in 2011 to 133 635 in 2031. The total per capita health care cost (excluding out-of-pocket expenses) for adults aged 20 and older in 2011 was about $16 800 for individuals with MS, and approximately $2500 for individuals without a neurological condition. Thus, after accounting for additional expenditures due to MS (excluding out-of-pocket expenses), total annual health sector costs for MS are expected to reach $2.0 billion by 2031. As well, the average out-of-pocket expenditure for people with MS was around $1300 annually throughout the projection period. MS is associated with a significant economic burden on society, since it usually affects young adults during prime career- and family-building years. Canada has a particularly high prevalence of MS, so research such as the present study is essential to provide a better understanding of the current and future negative impacts of MS on the Canadian population, so that health care system policymakers can best plan how to meet the needs of patients who are affected by MS. These findings also suggest that identifying strategies to prevent MS and more effectively treat the disease are needed to mitigate these future impacts.

A population-based study comparing multiple sclerosis clinic users and non-users in British Columbia, Canada.

Background and purposeMuch clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non‐users of the specialty MS clinics in British Columbia, Canada.MethodsThis was a retrospective record‐linkage cohort study using prospectively collected data from the British Columbia Multiple Sclerosis database and province‐wide health administrative databases.ResultsThere were 2841 incident MS cases between 1996 and 2004 including 1648 (58%) that had registered at an MS clinic (‘clinic cases’) and 1193 (42%) that had not (‘non‐clinic cases’). Gender and socioeconomic status distributions were similar; however, non‐clinic cases were older, accessed health services more frequently and had a higher burden of comorbidity than clinic cases. Only 1% of the non‐clinic cases had filled a prescription for an MS‐specific disease‐modifying therapy, compared to 51% of the clinic cases.ConclusionsOur findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic‐based MS cohorts may not always be generalizable to the wider MS population; and access to population‐based health administrative data offers the opportunity to gain a broader understanding of MS.

Sex differences in comorbidity at diagnosis of multiple sclerosis: A population-based study.

Objective:To determine the prevalence of comorbidity in the multiple sclerosis (MS) population at the time of MS diagnosis. We also compared the prevalence of comorbidity in the MS population to that in a matched cohort from the general population.Methods:Using population-based administrative health data from 4 Canadian provinces, we identified 23,382 incident MS cases and 116,638 age-, sex-, and geographically matched controls. We estimated the prevalence of hypertension, diabetes, hyperlipidemia, heart disease, chronic lung disease, epilepsy, fibromyalgia, inflammatory bowel disease, depression, anxiety, bipolar disorder, and schizophrenia at MS diagnosis using validated case definitions. We compared the populations using rate ratios.Results:Of the MS cases, 16,803 (71.9%) were female. The most prevalent comorbidity was depression (19.1%). Compared to the matched population, all comorbidities except hyperlipidemia were more common in the MS population. Relative to the matched populations, the prevalence of hypertension was 16% higher for women with MS and 48% higher for men with MS, thus there was a disproportionately higher prevalence of hypertension in men with MS than women. Men with MS also had a disproportionately higher prevalence than women with MS for diabetes, epilepsy, depression, and anxiety.Conclusions:Comorbidity is more common than expected in MS, even around the time of diagnosis. The prevalence of psychiatric comorbidity is particularly high and highlights the need for clinical attention to this issue. The observed sex-specific differences in the burden of comorbidity in MS, which differ from those in the matched population, warrant further investigation.

Epidemiology of multiple sclerosis: results from a large observational study in the UK.

Multiple sclerosis (MS) progression to mortality may not be solely determined by the underlying autoimmune process. We conducted a study in a large cohort of MS patients with the aim of describing characteristics of MS patients and identification of predictors for all-cause mortality in this patient group. We performed a retrospective analysis of primary care data from the UK Clinical Practice Research Datalink. Incident MS cases diagnosed between 1993 and 2006 were identified and validated using electronic and original medical records. Patients were followed to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional regression with age as time-scale. In total, 1713 incident MS cases were identified. Following MS diagnosis, frequent comorbidities were infections (80 %), and depression (46 %). Adjusted HRs (95 % CIs) for all-cause mortality were: 2.0 (1.2–3.4) for current smoking; 7.6 (3.2–17.7) for alcohol abuse; 2.7 (1.6–4.5) for pneumonia and influenza; 4.1 (2.7–6.3) for urinary tract infections; 2.2 (1.2–4.2) for heart disease and 4.9 (2.9–8.0) for cancer. Our results suggest that MS survival is influenced not only by the underlying autoimmune process, but also by patient comorbidities and lifestyle factors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-015-7796-2) contains supplementary material, which is available to authorized users.

Health care utilization before and after intensive care unit admission in multiple sclerosis

ObjectivesThe incidence of intensive care unit (ICU) admission is elevated in the multiple sclerosis (MS) population but the reasons for this are incompletely understood, as are outcomes post-ICU admission. Among MS patients we examined the association between ICU admission and health care utilization in the year preceding admission, and compared health care utilization following ICU admission among persons with MS and persons from the general population. MethodsWe used population-based administrative data from Manitoba, Canada to identify 4237 MS cases of which 2547 were incident. We compared the incidence rates of ICU admission in the prevalent MS population according to health care utilization in the year before admission, adjusting for age, sex, comorbidity and socioeconomic status. Among incident cases of MS we compared rates of health care utilization after ICU admission to those in a matched general population cohort. We used generalized linear models adjusting for age, sex, socioeconomic status, region, comorbidity and utilization before admission. ResultsOf 4219 prevalent MS cases, 222 (5.3%) were admitted to the ICU. After adjustment, any hospitalization in the prior year conferred an 80% increased incidence, and physician visits in the highest tertile and prescription costs in the highest quartile in the prior year each conferred a more than two-fold increased incidence of admission. Among 2547 incident cases of MS, 109 (4.3%) were admitted to the ICU and 93 survived their admission. Thirty-eight percent of the MS population were re-hospitalized in the year following admission, similar to the matched population (33.8%). Seven percent of both populations were readmitted to the ICU. The MS population had more hospital days after ICU admission than the matched population (adjusted RR 3.11; 95% CI: 1.34–5.90). After adjustment the number of physician visits did not differ between populations. ConclusionsThe incidence of ICU admission is higher among persons with MS who have higher prior health care utilization. Health care utilization remains high after ICU admission. Efforts to prevent ICU admission in this population are needed.

Expanding the use of administrative claims databases in conducting clinical real-world evidence studies in multiple sclerosis

Objective:Administrative claims databases provide a wealth of data for assessing the effect of treatments in clinical practice. Our aim was to propose methodology for real-world studies in multiple sclerosis (MS) using these databases.Research design and methods:In three large US administrative claims databases: MarketScan, PharMetrics Plus and Department of Defense (DoD), patients with MS were selected using an algorithm identified in the published literature and refined for accuracy. Algorithms for detecting newly diagnosed (‘incident’) MS cases were also refined and tested. Methodology based on resource and treatment use was developed to differentiate between relapses with and without hospitalization.Results:When various patient selection criteria were applied to the MarketScan database, an algorithm requiring two MS diagnoses at least 30 days apart was identified as the preferred method of selecting patient cohorts. Attempts to detect incident MS cases were confounded by the limited continuous enrollment of patients in these databases. Relapse detection algorithms identified similar proportions of patients in the MarketScan and PharMetrics Plus databases experiencing relapses with (2% in both databases) and without (15–20%) hospitalization in the 1 year follow-up period, providing findings in the range of those in the published literature.Limitation:Additional validation of the algorithms proposed here would increase their credibility.Conclusions:The methods suggested in this study offer a good foundation for performing real-world research in MS using administrative claims databases, potentially allowing evidence from different studies to be compared and combined more systematically than in current research practice.

Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk.

Background: The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype.Methods: We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction.Results: An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (AP 0.3, 95% CI 0.02–0.5 in the incident study, and AP 0.4, 95% CI 0.1–0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A*02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3–6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5–10.8).Conclusions: The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.

Neonatal vitamin D status and risk of multiple sclerosis.

Low vitamin D status at birth may be associated with risk of adult onset multiple sclerosis, but this link has not been studied directly. We assessed the relation between neonatal vitamin D concentrations, measured in stored blood samples, and risk of multiple sclerosis. This was a population-based case-control study in Sweden including 459 incident cases of multiple sclerosis and 663 controls, randomly drawn from a national population registry and frequency matched on sex, age, and residential area. There was no association between neonatal 25-hydroxyvitamin D quintile and risk of multiple sclerosis (crude odds ratio = 1.0, 95% confidence interval = 0.68-1.44, for the highest quintile compared to the lowest). Adjusting for a number of potential confounding factors in early life (month of birth, latitude of birth, breastfeeding) and in adult life (25-hydroxyvitamin D, sun exposure, vitamin D intake from dairy products, fatty fish consumption, smoking, body mass index at 20 years of age) as well as ancestry, multiple sclerosis heredity, and socioeconomic group did not considerably affect the result. At a broad population level, 25-hydroxyvitamin D at birth was not associated with risk of multiple sclerosis.

Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors

To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.

Alcohol as a Modifiable Lifestyle Factor Affecting Multiple Sclerosis Risk

Alcohol consumption may be a modifiable lifestyle factor that affects the risk of developing multiple sclerosis (MS). Results of previous studies have been inconsistent. To investigate the possible association of alcohol consumption with the risk of developing MS and to relate the influence of alcohol to the effect of smoking. This report is based on 2 case-control studies: Epidemiological Investigation of Multiple Sclerosis (EIMS) included 745 cases and 1761 controls recruited from April 2005 to June 2011, and Genes and Environment in Multiple Sclerosis (GEMS) recruited 5874 cases and 5246 controls between November 2009 and November 2011. All cases fulfilled the McDonald criteria. Both EIMS and GEMS are population-based studies of the Swedish population aged 16 to 70 years. In EIMS, incident cases of MS were recruited via 40 study centers, including all university hospitals in Sweden. In GEMS, prevalent cases were identified from the Swedish national MS registry. In both studies, controls were randomly selected from the national population register, matched by age, sex, and residential area at the time of disease onset. Multiple sclerosis status. There was a dose-dependent inverse association between alcohol consumption and risk of developing MS that was statistically significant in both sexes. In EIMS, women who reported high alcohol consumption had an odds ratio (OR) of 0.6 (95% CI, 0.4-1.0) of developing MS compared with nondrinking women, whereas men with high alcohol consumption had an OR of 0.5 (95% CI, 0.2-1.0) compared with nondrinking men. The OR for the comparison in GEMS was 0.7 (95% CI, 0.6-0.9) for women and 0.7 (95% CI, 0.2-0.9) for men. In both studies, the detrimental effect of smoking was more pronounced among nondrinkers. CONCLUSIONS AND RELEVANCE; Alcohol consumption exhibits a dose-dependent inverse association with MS. Furthermore, alcohol consumption is associated with attenuation of the effect of smoking. Our findings may have relevance for clinical practice because they give no support for advising patients with MS to completely refrain from alcohol.

Fatty fish intake is associated with decreased occurrence of multiple sclerosis

Background: High vitamin D levels have been associated with a decreased risk of developing multiple sclerosis (MS). The most important source of dietary vitamin D is fatty fish. Objective: The objective of this paper is to investigate the association between fish consumption and the risk of MS, including the interaction between fish intake and ultraviolet radiation (UVR) exposure habits. Methods: This study is based on the project Epidemiological Investigation of MS (EIMS), which is a Swedish population-based case-control study. The analysis included 1879 incident cases of MS and 4135 controls. Subjects who reported high fatty fish intake were compared regarding occurrence of MS with those who reported low intake by calculating odds ratio (OR) with 95% confidence interval (CI). Results: Frequent fatty fish intake was associated with decreased occurrence of MS (adjusted OR 0.82 (95% CI 0.68-0.98). There was no significant association between intake of lean fish and MS. Conclusion: Fatty fish intake might decrease the risk for MS. A hypothetical explanation is that intake of fatty fish may compensate for vitamin D deficiency that is associated with increased MS risk.

Exploring the Implications of Small-Area Variation in the Incidence of Multiple Sclerosis

In this study, we describe the geospatial variation in the incidence of multiple sclerosis (MS) in Manitoba, Canada, and the sociodemographic characteristics associated with MS incidence. By using administrative health data, we identified all incident cases of MS in Manitoba from 1990 to 2006 (n = 2,290) and geocoded them to 230 neighborhoods in the City of Winnipeg and 268 municipalities in rural Manitoba. Age-standardized incidence rates for 1990-2006 (combined) were calculated for each region. By using the spatial scan statistic, we identified high-rate clusters in southwestern (incidence rate ratio (IRR) = 1.48) and central Winnipeg (IRR = 1.54) and low-rate clusters in north-central Winnipeg (IRR = 0.52) and northern Manitoba (IRR = 0.48). Multivariable Poisson regression showed a positive association between MS incidence rates and socioeconomic status. Despite our finding that MS incidence varied geographically and by socioeconomic status, the low Gini coefficient of 0.152 for MS incidence identified in this study suggests that the causes of MS are pervasive across all population groups. Searching for local-level causes of the disease may therefore not be as productive as investigating etiological factors operating at the population level. This may require an examination of macro-level differences in environmental exposures between high- and low-incidence regions of the world.

Reverse causality behind the association between reproductive history and MS

Background: Possible associations between childbearing patterns and multiple sclerosis (MS) risk have been studied for a long time, with conflicting results. We aimed to investigate the influence of reproductive history on MS risk. Methods: Using a Swedish population-based case-control study involving incident cases of MS (1798 cases, 3907 controls), we calculated odds ratios (OR) for MS comparing parents with childless subjects together with 95% confidence intervals (CI) employing logistic regression. Results: Overall, there was an association between having children and reduced MS risk among both sexes. Subjects who had become parents within five years prior to the index year had a substantially reduced risk of developing MS (OR 0.6, 95% CI 0.5–0.8 for women, and OR 0.4, 95% CI 0.3–0.6 for men). No association between having children and MS risk was observed when more than 10 years had passed since the birth of the last child. We found no association between increasing offspring number and MS risk. Conclusions: The observed association between reproductive history and MS risk is restricted to a limited time period preceding the index year, with similar findings in both sexes, which contradicts biologic impact of pregnancy on MS risk and argues in favor of reverse causality, i.e. that fecundity is affected by yet-undiagnosed MS.

Epstein-Barr Virus, Hygiene, and Multiple Sclerosis in Mexico City

Background/Aims: We studied whether serological antibody titers against Epstein-Barr virus (EBV) were related to multiple sclerosis (MS) risk in Mexico City, a population undergoing an epidemiological transition. Additionally, we explored the association between markers of hygiene and intestinal parasite infection and MS prevalence. Methods: We conducted a hospital based case-control study in Mexico City; 52 incident MS cases. Childhood and adult hygiene scores were created using information from questionnaires. 51 cases and 51 controls provided blood samples for biomarker analyses. Results: There was a 3-fold increase in risk of MS with each 1 unit increase in anti-EBNA1 titer (OR 3.02, 95% CI: 1.01-9.02). Increasing childhood and adult hygiene scores were associated with a modestly increased risk of MS (ORchildhood 1.20, 95% CI: 1.04-1.38; ORadult 1.28, 95% CI: 1.04-1.58). We found no association between antibody titer to neither Stronglyloides nor Ascaris and MS risk. Conclusion: High anti-EBNA1 antibody titers appears to be associated with increased MS risk even in a region where MS had historically low incidence and infectious mononucleosis is rare, providing further support for the postulated role of EBV in MS etiology. We also found moderate support for a role of higher ‘hygiene’ being associated with susceptibility to MS.

Incidence of Multiple Sclerosis in the General Population in the Netherlands, 1996–2008

Background: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. Methods: A retrospective cohort study (1996–2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. Results: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2–7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3–5) in 1996–2004 to 9/100,000 py in 2007/8 (95% CI, 6–16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). Conclusions: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.

Estimated Incidence of Multiple Sclerosis Among United States Armed Forces Personnel Using the Defense Medical Surveillance System

The comprehensive longitudinal medical records of the U.S. Armed Forces provide a valuable tool to study the epidemiology of multiple sclerosis (MS) in persons from a diverse demography. This study's objectives were to estimate the frequencies, incidence rates (IRs), trends, and correlates of MS among active component U.S. military members from 2000 to 2009. An International Classification of Diseases, 9th Revision, code algorithm was used to identify MS cases from the Defense Medical Surveillance System database. IRs were determined by dividing the number of cases of MS by the total person-time of the active component during each year. During the 10-year period, there were 1,827 incident cases of MS with an overall IR of 12.9 per 100,000 person-years (p-yrs). Black non-Hispanics had a higher IR: (18.3 per 100,000 p-yrs) than White non-Hispanics (12.5 per 100,000 p-yrs). The incidence of MS by birth month and geographic home did not show a clear trend of seasonality or latitudinal gradient. This investigation is the first longitudinal study of MS incidence in U.S. Armed Forces personnel. The study demonstrates higher IRs than seen in other populations and reveals a novel pattern of MS incidence by race.

Sunlight is associated with decreased multiple sclerosis risk: no interaction with human leukocyte antigen‐DRB1*15

Both insufficient exposure to sunlight and vitamin D deficiency have been associated with an increased risk for multiple sclerosis (MS). An interaction between human leukocyte antigen HLA-DRB1*15 and vitamin D in MS was recently proposed. We investigated the association between previous exposure to ultraviolet radiation (UVR), vitamin D status at inclusion in the study, and MS risk including the interaction of these factors with HLA-DRB1*15. A population-based case-control study involving 1013 incident cases of MS and 1194 controls was performed in Sweden during 2005-2010. Subjects were classified according to their UVR exposure habits, vitamin D status, and HLA genotypes. The associations between different sun exposure habits/vitamin D levels and MS were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. Potential interaction was evaluated by calculating the attributable proportion due to interaction. Subjects with low UVR exposure had a significantly increased risk of MS compared with those who reported the highest exposure (OR 2.2, 95% CI 1.5-3.3). Similarly, subjects who had 25-hydroxy-vitamin D levels less than 50 nM/l had an increased risk for MS (OR 1.4, 95% CI 1.2-1.7). The association between UVR exposure and MS risk persisted after adjustment for vitamin D status. There was no interaction with HLA-DRB1*15 carriage. UVR and vitamin D seem to affect MS risk in adults independently of HLA-DRB1*15 status. UVR exposure may also exert a protective effect against developing MS via other pathways than those involving vitamin D.

Exposure to environmental tobacco smoke is associated with increased risk for multiple sclerosis

Background: Tobacco smoking has consistently been associated with increased risk for multiple sclerosis. However, data has been inconsistent regarding the influence of passive smoking. Objective: The aim was to estimate the influence of passive smoking on the risk for multiple sclerosis. Methods: A population-based case–control study using incident cases of multiple sclerosis was performed in Sweden, and the study population was restricted to subjects who had never smoked (695 cases, 1635 controls). The incidence of multiple sclerosis among never-smokers who had been exposed to passive smoking was compared with that of never-smokers who had never been exposed by calculating the odds ratio with a 95% confidence interval employing logistic regression. Results: The risk for multiple sclerosis was increased among never-smokers who had been exposed to passive smoking (OR 1.3, 95% CI 1.1–1.6) compared to never-smokers who had never been exposed. The risk increased with increasing duration of exposure (p = 0.003). Conclusions: Exposure to environmental tobacco smoke is associated with an increased risk for multiple sclerosis. Since smoking, but not usage of oral tobacco in the form of moist snuff, is associated with increased risk for multiple sclerosis, we consider that the critical effects of passive smoking may be the result of irritations in the lungs. Hence, further studies would be valuable in order to clarify whether other forms of lung irritation, such as air pollution, contribute to the triggering of multiple sclerosis.

Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis

Both genetic and environmental factors display low or modest associations with multiple sclerosis. Hypothetically, gene-environment interactions may exert much stronger effects. In this study, we investigated potential interactions between genetic risk factors and smoking in relation to risk of developing multiple sclerosis. A population-based case-control study involving incident cases of multiple sclerosis (843 cases, 1209 controls) was performed in Sweden. Cases and controls were classified according to their smoking status and human leukocyte antigen DRB1 as well as human leukocyte antigen A genotypes. Subjects with different genotypes and smoking habits were compared with regard to incidence of multiple sclerosis, by calculating odds ratios with 95% confidence intervals employing logistic regression. The potential interaction between different genotypes, as well as between genotype and smoking, was evaluated by calculating attributable proportion due to interaction. A significant interaction between two genetic risk factors, carriage of human leukocyte antigen DRB1*15 and absence of human leukocyte antigen A*02, was observed among smokers whereas such an interaction was absent among non-smokers. There were considerable differences in odds ratios between the various groups. Compared with non-smokers with neither of the genetic risk factors, the odds ratio was 13.5 (8.1-22.6) for smokers with both genetic risk factors. The odds ratio for smokers without genetic risk was 1.4 (0.9-2.1) and the odds ratio for non-smokers with both genetic risk factors was 4.9 (3.6-6.6). Among those with both genetic risk factors, smoking increased the risk by a factor of 2.8 in comparison with a factor of 1.4 among those without the genetic risk factors. The risk of developing multiple sclerosis associated with human leukocyte antigen genotypes may be strongly influenced by smoking status. The findings are consistent with our hypothesis that priming of the immune response in the lungs may subsequently lead to multiple sclerosis in genetically susceptible people.

Dietary intake of vitamin D during adolescence and risk of multiple sclerosis

Adolescence may be an important etiological period in the development of multiple sclerosis (MS), and studies suggest that adequate vitamin D nutrition is protective. Here, the authors examined whether dietary intake of vitamin D during adolescence decreases the risk of MS in adulthood. In 1986 in the Nurses' Health Study and in 1998 in the Nurses' Health Study II (NHSII), women completed a food frequency questionnaire regarding their dietary intake during adolescence. From this, daily intake of vitamin D was calculated. Adolescent diet was available for 379 incident MS cases confirmed over the combined 44 years of follow-up in both cohorts, and for 67 prevalent cases in the NHSII who had MS at baseline (1989). Cox proportional hazards models were used to calculate relative risk estimates and 95% confidence intervals. Total vitamin D intake during adolescence was not associated with MS risk. Intake of ≥ 400 IU/day of vitamin D from multivitamins was associated with a non-statistically significant reduced risk (RR compared to no intake = 0.73, 95% CI: 0.50-1.07, P = 0.11), whereas intake of whole milk, an important source of dietary vitamin D, was associated with an increased risk. The possibility of opposite effects of vitamin D and milk intake on MS risk should be considered in future studies.