Triggers in MSThursday, October 03, 2013, 15:31 - 15:43
High body mass index and alcohol consumption at age 15-19 and previous mononucleosis are important factors for age at onset in Danish multiple sclerosis patientsA.B. Oturai, J. Hejgaard, F. Sellebjerg, A. Albrectsen, E. Petersen, N. Koch-Henriksen, P. Sørensen, H.B. Sondergaard (Copenhagen, DK)
Background: There is compelling evidence that both genetic and environmental/lifestyle factors confer susceptibility to develop multiple sclerosis (MS). However, the influence of these factors on clinical phenotypes, e.g., age at disease onset has only incompletely been studied.
Objective: To determine the most important genetic and environmental/lifestyle factors for age at disease onset in Danish MS patients.
Methods: Blood samples for DNA analysis and a comprehensive environmental/lifestyle questionnaire were collected from ethnically Danish MS patients from the whole of Denmark in the period 2010 and 2012. Among 1486 patients 1383 (990 females, 393 males) had completed data sets for the investigated parameters and were thus eligible for inclusion.
We tested the predictive value for age of MS onset for: body mass index at age 20 (BMI < 18.5, 18.5-25, >25); smoking habits between age 15-19 (never smokers, regular smokers for more than one year (1-5 cigarettes daily), regular smokers for more than one year (5 > cigarettes daily); alcohol consumption between age 15-19 (never drinking alcohol, drinking 1-5 units per week, drinking >5 units per week); sex; previous mononucleosis; education; HLA-DRB1*15:01 (rs9271366) and HLA-A*02:01 (rs2975033). All factors were included in a multivariate regression analysis and the least significant variables were sequentially removed until only significantly associated factors (p<0.05) remained.
Results: Outcome is given in adjusted effect sizes, as number of years the factor lowers age at onset. The most important factors for reducing age at disease onset were: high BMI at age 20 by 3.60 years (p=0.001); previous mononucleosis by 2.50 years (p=0.001); high alcohol consumption by 2.49 years (p=0.00005); and homozygosity for HLA-DRB1*15:01 by 1.90 years (p=0.027). All factors, except HLA-DRB1*15:01, were still significant after Bonferroni correction.
Conclusions: High BMI at age 20, previous mononucleosis and high alcohol consumption between age 15-19 are the most important known factors for lowering age at onset in Danish MS patients.
Annette Oturai has served on scientific advisory boards for Novartis, and served as consultant for Biogen Idec; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; has received speaker honoraria from, Biogen Idec, Novartis, and Sanofi-Aventis. Her laboratory has received research support from Biogen Idec and Novartis.
Finn Sellebjerg has served on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva, has been on the steering committee of a clinical trial sponsored by Merck Serono, and served as consultant for Biogen Idec and Novo Nordisk; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; has received speaker honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Schering-Plough. His laboratory has received research support from Biogen Idec, Bayer Schering, Merck Serono, Sanofi-Aventis and Novartis.
Per Soelberg Sorensen has served on scientific advisory boards Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, Elan, GSK, has been on steering committees or independent data monitoring boards in clinical trials sponsored by Merck Serono, Genmab, TEVA, GSK, Bayer Schering, and he has received funding of travel for these activities; has served as Editor-in-Chief of the European Journal of Neurology, and is currently editorial board member for Multiple Sclerosis Journal, European Journal of Neurology, Therapeutic Advances in Neurological Disorders and; has received speaker honoraria from Biogen Idec, Merck Serono, TEVA, Bayer Schering, Sanofi-aventis, Genzyme, and Novartis; and has received payment for writing and reviewing manuscript from IBI Consulting, a division of Informa plc. His department has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, from the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health.
Nils Koch-Henriksen has received honoraria for lecturing and attending advisory boards and unrestricted grants from Biogen Idec, Novartis, and Teva for the Danish MS Treatment Register.
Julie Hejgaard has nothing to disclose. Eva Petersen has nothing to disclose. Anders Albrectsen has nothing to disclose. Helle Bach Søndergaard has nothing to disclose.