Pathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis

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dc.contributor.authorJohannes, Clinten_ZA
dc.contributor.authorMoremi, Kelebogile E.en_ZA
dc.contributor.authorKemp, Merlisa C.en_ZA
dc.contributor.authorWhati, Lindiween_ZA
dc.contributor.authorEngel- Hills, Penelopeen_ZA
dc.contributor.authorKidd, Martinen_ZA
dc.contributor.authorvan Toorn, Ronalden_ZA
dc.contributor.authorJaftha, Mariaanen_ZA
dc.contributor.authorJanse van Rensburg, Susanen_ZA
dc.contributor.authorKotze, Maritha J.en_ZA
dc.date.accessioned2023-04-24T09:17:40Z
dc.date.available2023-04-24T09:17:40Z
dc.date.issued2023-05-17
dc.descriptionThe original publication is available at https://www.tandfonline.com/journals/ipme20en_ZA
dc.description.abstractBackground: Lipid metabolism may impact disability in people with multiple sclerosis (pwMS). Methods: Fifty-one pwMS entered an ultrasound and MRI study, of whom 19 had followed a pathology- supported genetic testing program for more than 10 years (pwMS-ON). Genetic variation, blood biochemistry, vascular blood flow velocities, diet and exercise were investigated. Results: PwMS-ON had significantly lower (p < 0.01) disability (Expanded Disability Status Scale) than pwMS not on the program (1.91 ± 0.75 vs 3.87 ± 2.32). A genetic variant in the lipid transporter FABP2 gene (rs1799883; 2445G>A, A54T) was significantly associated (p < 0.01) with disability in pwMS not on the program, but not in pwMS-ON (p = 0.88). Vascular blood flow velocities were lower in the presence of the A-allele. Conclusion: Pathology-supported genetic testing may provide guidance for lifestyle interventions with a significant impact on improved disability in pwMS. Plain Language Summary This study investigated the role of a genetic variant that increases saturated fat absorption and may make people with multiple sclerosis (MS) more susceptible to disability progression. Of 51 people with MS, 19 had followed a program which includes normalization of blood test results and daily intake of unsaturated fatty acids for more than 10 years, while the others had not. The latter group had significantly greater disability than the people who had followed the program, suggesting that the unsaturated fatty acids modulated the effect of the genetic variant. Six MS cases are presented as examples, including a marathon athlete (Case 1) and a patient who showed a dramatic decrease in disability from being wheelchair-bound for 15 years to walking freely (Case 2). Executive Summary: • In order to investigate the conundrum of why some people with multiple sclerosis (pwMS) become disabled while others do not, a cross-sectional interdisciplinary study was initiated from 1996 to the present at Stellenbosch University, to record data into a database regarding genetic variations, blood biochemistry, diet and exercise. Pathology-supported genetic testing (PSGT), a practical method to apply personalized medicine, was implemented to elucidate potential modulation of genetic variations through lifestyle interventions toward prevention of disability in pwMS. • The Gknowmix.org database is used to translate information obtained from a comprehensive study into personalized reports containing guidelines for treatment of pwMS by clinicians and supporting healthcare professionals, which enables P4 medicine: participatory (patient), personalized (scientist), predictive (clinician) and preventive (dietitian). • In the present case–control sub-study, 51 pwMS and 25 controls volunteered for an ultrasound and MRI study. Of these pwMS, 19 had followed the PSGT lifestyle program for more than 10 years, which included normalization of blood biochemistry, dietary intervention and exercise, as well as daily intake of specific supplements (the Rapha Regimen) [3], including unsaturated fatty acids (omega-3 and evening primrose oil). • The 19 pwMS who had followed the program had significantly less disability (p < 0.01), as assessed with the Expanded disability status scale (EDSS), than those who had not followed the program (1.91 ± 0.75 vs 3.87 ± 2.32). Furthermore, in the pwMS who had not followed the program, a genetic variant of a lipid transporter which favors increased absorption of saturated fatty acids, FABP2 rs1799883 (2445G>A, A54T), was associated significantly (p < 0.01) with the EDSS, while in the pwMS who had followed the program there was no association (p = 0.88). There was no difference in allele frequency between pwMS and controls. • Ultrasound assessments showed that higher blood flow velocities in the right common carotid arteries and vertebral arteries were significantly associated with improved EDSS, while the FABP2 rs1799883 variant was associated with decreased blood flow. • In the pwMS, homocysteine was significantly inversely associated with folate intake (p < 0.01). In the controls, saturated/trans fat intake was significantly associated with BMI (p < 0.01). • Six MS cases selected randomly are presented to demonstrate how data integration was instrumental in elucidating how dietary unsaturated fat intake may modulate the effect of FABP2 rs1799883 toward prevention of disability in pwMS who followed the PSGT protocol over more than 10 years. Of these, Case 1 is a marathon athlete, and Case 2 showed a dramatic decrease in EDSS from 7.5 to 2.0 over more than 10 years.en_ZA
dc.description.urihttps://www.futuremedicine.com/doi/full/10.2217/pme-2022-0016
dc.description.versionpost-print
dc.identifier.citationJohannes, C, Moremi, KE, Kemp MC, Whati, L, Engel-Hills, P, Kidd, M, Van Toorn, R, Jaftha, M, J van Rensburg, S, & Kotze, MJ. 2023. Pathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis. Personalized Medicine, 20(2):107-130. https://doi.org/10.2217/pme-2022-0016.en_ZA
dc.identifier.doihttps://doi.org/10.2217/pme-2022-0016
dc.identifier.issn1744-828X (online)
dc.identifier.issn1741-0541 (print)
dc.identifier.orcidhttps://orcid.org/0009-0002-4358-9495
dc.identifier.orcidhttps://orcid.org/0000-0003-1105-1578
dc.identifier.orcidhttps://orcid.org/0000-0001-5126-6982
dc.identifier.orcidhttps://orcid.org/0000-0002-1084-769X
dc.identifier.orcidhttps://orcid.org/0000-0002-2689-065X
dc.identifier.orcidhttps://orcid.org/0000-0003-2929-0972
dc.identifier.orcidhttps://orcid.org/0000-0002-2437-8978
dc.identifier.orcidhttps://orcid.org/0000-0002-6050-2876
dc.identifier.urihttp://hdl.handle.net/10019.1/126813
dc.language.isoen_ZAen_ZA
dc.rights.holderFuture Medicine
dc.subjectMultiple sclerosisen_ZA
dc.subject.namePersonalized Medicine
dc.subject.namePathology-supported genetic testing
dc.subject.nameEDSS
dc.subject.namedisability
dc.subject.namevascular ultrasound
dc.subject.nameFABP2 genetic variant
dc.subject.nameunsaturated fatty acids
dc.titlePathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosisen_ZA
dc.typeArticleen_ZA
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