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


Zhang, Y and Zhou, Y and van der Mei, IAF and Simpson, S and Ponsonby, A-L and Lucas, RM and Tettey, P and Charlesworth, J and Kostner, K and Taylor, BV, Ausimmune/AusLong Investigators Group, 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. ISSN 0022-3050 (2019) [Refereed Article]

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

DOI: doi:10.1136/jnnp-2018-319870


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=1.410-6), 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 Details

Item Type:Refereed Article
Keywords:genetic polymorphism, lipid profile, multiple sclerosis
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Zhang, Y (Mr Ben Zhang)
UTAS Author:Zhou, Y (Mr Yuan Zhou)
UTAS Author:van der Mei, IAF (Professor Ingrid van der Mei)
UTAS Author:Simpson, S (Dr Steve Simpson JR)
UTAS Author:Tettey, P (Mr Prudence Tettey)
UTAS Author:Charlesworth, J (Dr Jac Charlesworth)
UTAS Author:Taylor, BV (Professor Bruce Taylor)
ID Code:131174
Year Published:2019
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-03-06
Last Modified:2020-03-04

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