Open Access Repository

Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis

Zhang, Yan ORCID: 0000-0001-9126-4922, Zhou, Y ORCID: 0000-0003-1962-2574, van der Mei, IAF ORCID: 0000-0001-9009-7472, Simpson Jr, S ORCID: 0000-0001-6521-3056, Ponsonby, AL, Lucas, RM, Tettey, P ORCID: 0000-0001-7461-2382, Charlesworth, J ORCID: 0000-0001-6201-3518, Kostner, K and Taylor, BV 2019 , 'Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis' , Journal of Neurology, Neurosurgery and Psychiatry , pp. 1-6 , doi: 10.1136/jnnp-2018-319870.

Full text not available from this repository.

Abstract

Objective: To investigate whether lipid-related or body mass index (BMI)-related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS).Methods: The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (pResults: Five lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (ptrend=1.4×10-6), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL; pinteraction=0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL; pinteraction=0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL.Interpretation: In this prospective cohort study, both lipid levels and lipid-related polymorphisms individually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.

Item Type: Article
Authors/Creators:Zhang, Yan and Zhou, Y and van der Mei, IAF and Simpson Jr, S and Ponsonby, AL and Lucas, RM and Tettey, P and Charlesworth, J and Kostner, K and Taylor, BV
Keywords: genetic polymorphism, lipid profile, multiple sclerosis
Journal or Publication Title: Journal of Neurology, Neurosurgery and Psychiatry
Publisher: B M J Publishing Group
ISSN: 0022-3050
DOI / ID Number: 10.1136/jnnp-2018-319870
Copyright Information:

Copyright 2019 Author(s) (or their employer(s))

Related URLs:
Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page
TOP