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J Neurol Neurosurg Psychiatry. 2019 Jun;90(6):636-641. doi: 10.1136/jnnp-2018-319870. Epub 2019 Feb 19.

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

Author information

1
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
2
Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
3
Murdoch Children's Research Institute, The University of Melbourne, Melbourne, Victoria, Australia.
4
National Centre for Epidemiology and Population Health, Research School of Population Health, College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia.
5
School of Public Health, University of Ghana, Accra, Ghana.
6
Mater Hospital, University of Queensland, Brisbane, Queensland, Australia.
7
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia bruce.taylor@utas.edu.au.

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 (p<0.05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression.

RESULTS:

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.

KEYWORDS:

genetic polymorphism; lipid profile; multiple sclerosis

PMID:
30782980
DOI:
10.1136/jnnp-2018-319870

Conflict of interest statement

Competing interests: A-LP received personal fees from Biogen Pty Ltd and the fees were used for travel and conference presentation. BVT has received travel grants and honoraria for presentations and Advisory Board membership from Biogen Pty Ltd, Merck Serona Ltd, Roche Pty Ltd Novartis Pty Ltd and Sanofi Pty Ltd.

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