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

Abstract

ObjectiveTo 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).MethodsThe 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.ResultsFive 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.InterpretationIn 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.

Cholesterol and neurodegeneration: longitudinal changes in serum cholesterol biomarkers are associated with new lesions and gray matter atrophy in multiple sclerosis over 5 years of follow‐up

“…Our findings are qualitatively consistent with, but complementary to, the recent report by Zhang et al who found that five lipid-modulating polymorphisms, rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862, were associated with disability worsening in MS [7]. However, because cholesterol is also regulated by environmental factors, our genetic findings and those of Zhang et al should be interpreted in this context with caution.…”

“…It is also important to understand the longitudinal changes in MS as cholesterol profiles change progressively during aging . Recently, disability worsening in MS patients over 5 years was reported as associated with interactions between baseline lipid levels and a cumulative genetic risk score . The goals of this research were to characterize and compare the longitudinal changes in cholesterol biomarkers in MS patients to healthy controls (HCs) over 5 years of follow‐up and to ascertain whether cholesterol changes in MS patients are associated with MRI measures of lesional damage and neurodegeneration.…”

The Relation between Eating Habits and Abdominal Fat, Anthropometry, PON1 and IL-6 Levels in Patients with Multiple Sclerosis

“…In addition, the lipid profile for both sexes is characterised by an intake of MUFA, PUFA and SFA that does not comply with the DRI [22], alongside a higher consumption of cholesterol in men, which is in line with other publications by other authors [33]. In this sense, certain studies have observed that there is a link between the dietary intake of lipids and a higher prevalence and progression of MS [34,35]. These eating habits (and derived anthropometric characteristics) may be related to variables associated with the disease itself.…”

Association between Lipoprotein Levels and Humoral Reactivity to Mycobacterium avium subsp. paratuberculosis in Multiple Sclerosis, Type 1 Diabetes Mellitus and Rheumatoid Arthritis

“…It is to be highlighted that the concentrations of HDL, LDL/VLDL and TC in MS patients were markedly elevated respect to HCs. Evidence has showed that HDL, LDL and TC variations were associated with MS progression [25,40,41]. For this reason, we performed an association analysis of serum HDL, LDL and TC levels and disability status in MS MAP+ and MAP- patients.…”