6533b82dfe1ef96bd12915a6
RESEARCH PRODUCT
Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis
Jan S. KirschkeReinhard HohlfeldJanine SchultzGisela AntonyRalf GoldPhilipp G. SämannTania KümpfelFelix LuessiRalf A. LinkerAnke SalmenChristiane GraetzUwe K. ZettlGerrit ToengesMark MühlauVinzenz FleischerJoachim HavlaViola BiberacherBernhard HemmerCarmen Infante-duarteAntje Jahn-eimermacherAchim BertheleMichael HeckerSteffen PfeufferF. WeberNelly SillerAdriane GrögerHeinz WiendlCarsten LukasFrauke ZippChristina M. LillSergiu GroppaDaniela ZöllerFriedemann PaulBarbara Bellenbergsubject
AdultMaleApolipoprotein EMultiple SclerosisAdolescentPolymorphism Single NucleotideBody Mass IndexYoung Adult03 medical and health sciencesApolipoproteins E0302 clinical medicineAtrophyMedizinische FakultätmedicineHumansSNPGenetic Predisposition to Disease030212 general & internal medicineddc:610Risk factorHLA-DRB1Agedbusiness.industryMultiple sclerosisSmokingNeurodegenerationBrainMiddle Agedmedicine.diseaseNeurologyImmunologyFemaleNeurology (clinical)AtrophybusinessBody mass index030217 neurology & neurosurgeryHLA-DRB1 Chainsdescription
Background: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. Objective: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. Methods: Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes. Results: Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters. Conclusions: Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients’ counseling upon initial diagnosis of MS.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-04-01 |