Lipid-related genetic polymorphisms modify the association between lipids and disability progression in multiple sclerosis (MS)
Author(s): ,
Y. Zhang
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS
Y. Zhou
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS
S. Simpson
Melbourne School of Population & Global Health, University of Melbourne, Melbourne, VIC, Australia
I. van der Mei
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS
B. Taylor
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS
ECTRIMS Online Library. Zhang Y.
Oct 12, 2018; 228913
Yan Zhang
Yan Zhang
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Abstract: P1072

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics

Background: An adverse serum lipid profile and increased body mass index (BMI) significantly predict a faster rate of disability progression in MS.
Objective: To investigate whether BMI- or lipid-related common genetic polymorphisms modulated this association.
Method: The association between disability progression (Expanded Disability Status Scale, EDSS change over 5 years) and BMI- or lipid-related genetic polymorphisms (identified from genome wide association analysis) were evaluated in a longitudinal cohort (n=186) who developed clinically definite MS post first demyelinating event. Serum lipids were measured at baseline. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (P< 0.05), and examined the interactions between the CGRS and lipid-related variables in predicting disability progression. All analyses were conducted using linear regression.
Results: Six lipid-related polymorphisms (rs2013208, rs9488822, rs17173637, rs9411489, rs10401969 and rs2277862) were nominally associated with disability progression whereas only one BMI polymorphism (rs2033529) was associated. The constructed lipid CGRS showed a significant, dose-dependent association with disability progression (ptrend=2.1×10-7), such that participants carrying 8 risk alleles progressed 0.35 EDSS points per year faster compared with those carrying ≤5. This CGRS model explained 25% of the variance in disability change in this cohort. We also found significant interactions between the CGRS and lipid-related variables in modulating disability progression, including high-density lipoprotein (Pinteraction=0.003), low-density lipoprotein (Pinteraction=0.021), total cholesterol to high-density lipoprotein ratio (Pinteraction< 0.001) and non-high-density lipoprotein (Pinteraction=0.024), such that an adverse lipid profile and an adverse lipid CGRS interacted to significantly worsen the rate of disability progression.
Conclusions: In this prospective cohort study, both lipids and lipid-related polymorphisms individually and jointly drove disability progression in MS. These results provide additional evidence in support of potentially modifiable lifestyle factors in MS progression, and these polymorphisms in particular may indicate potential points of intervention to moderate disability progression.
Disclosure: Yan Zhang: nothing to disclose
Yuan Zhou: nothing to disclose
Steve Simpson: nothing to disclose
Ingrid van der Mei: nothing to disclose
Bruce Taylor: nothing to disclose

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