Investigations in the Hungarian Multiple Sclerosis Patient Population: New Data on the Genetic Background and Validation of the Fatigue Impact Scale

MD Losonczi Erika
Investigations in the Hungarian Multiple Sclerosis Patient Population: New Data on the Genetic Background and Validation of the Fatigue Impact Scale.
Doktori értekezés, Szegedi Tudományegyetem.

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Summary Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The disease is heterogeneous, which results in different clinical manifestations. In the majority of MS patients, the disease begins with a relapsing course (relapsing-remitting form, RRMS), characterized by relapses and remissions, and followed by a progressive phase (secondary progressive MS, SPMS). In a smaller subset of patients, the relapsing phase is not observed and the disease progresses from the beginning (primary progressive form, PPMS). The appearance of the disease is determined by a combination of exogenous factors and the genetic background. Two of the genes whose potential association emerged from the analyses published previously by our MS Workgroup were selected for further analysis: • Tumour necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of infectious and autoimmune disorders, including MS. The human TNF gene maps to chromosome 6p21.3 in the highly polymorphic MHC region. The chromosome location suggests that TNF α single nucleotide polymorphisms (SNPs) may be involved in influencing the disease course during MHC-associated diseases such as MS. • Apolipoprotein E (ApoE), an important glycoprotein in the transport, uptake and redistribution of cholesterol, is necessary in nerve tissue repair. The APOE gene (APOE) is involved in neurodegenerative diseases, the best-known association being that between the APOE ε4 allele and Alzheimer’s disease. Our primary aims were a multicentre assessment of the possible influence of the TNF-α -376 polymorphism and of the APOE gene on the susceptibility to PPMS in Hungary. Polymerase chain reaction and restriction fragment length polymorphism were carried out on 45 PPMS patients, 45 age and sex-matched RRMS patients and 45 healthy controls (HCs). In our study, the GG genotype and the guanine allele (G) in the TNF-α gene at position -376 were detected significantly more often in the PPMS group than in the HC group. As regards the APOE gene, the number of PPMS patients without the ε2 allele was found to be notably high, whilst the ε2 allele was overrepresented in the RRMS group. A markedly high frequency of the ε4 allele was found in the PPMS group and a very low frequency in the HC group. As concerns the clinical parameters, significant differences were observed between the RRMS and PPMS groups. Differences were also detected regarding the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) scores when the patients were grouped according to the presence or absence of the ε2 allele. All of the observed differences in the clinical parameters disappeared when the patients were further stratified according to the type of MS. Our findings suggest that the G allele at position -376 of the TNF-α gene may be one of the factors responsible for progression in PPMS, and that the presence of the ε2 and ε4 alleles may play a role in the development of the disease. However, when any type of the disease has already developed, the alleles show no association with the clinical parameters. In addition to the genetic investigations, as a secondary aim we intended to better understand fatigue a very important feature of MS. Fatigue is one of the most frequent complaints of patients with MS. The Fatigue Impact Scale (FIS), one of the 30 available fatigue questionnaires, is commonly applied because it evaluates multidimensional aspects of fatigue. An objective questionnaire for evaluation of the impact of fatigue in Hungarian MS patients has not yet been approved. On the basis of our previous experience with the adaptation and validation process of the Multiple Sclerosis Quality of Life Instrument, we set out to test the validity, test-retest reliability and internal consistency of the Hungarian version of the FIS. One hundred and eleven MS patients and 85 HCs completed the FIS and the Beck Depression Inventory (BDI), a large majority of them on 2 occasions, 3 months apart. The total FIS score and subscale scores differed statistically between the MS patients and the HCs in both FIS sessions. In the test-retest reliability assessment, the ICCs were statistically high in both the MS and HC groups. Cronbach’s alpha values were also notably high. Consequently, our results indicate that the FIS can be regarded as a valid and reliable scale with which to improve our understanding of the impact of fatigue on the health-related quality of life in MS patients without severe disability.

Mű típusa: Disszertáció (Doktori értekezés)
Doktori iskola: Klinikai Orvostudományok Doktori Iskola
Tudományterület / tudományág: orvostudományok > klinikai orvostudományok
Magyar cím: Vizsgálatok a magyarországi szklerózis multiplexes beteg populációban: új adatok a genetikai háttérhez valamint a Fatigue Impact Scale validálása
Idegen nyelvű cím: Investigations in the Hungarian Multiple Sclerosis Patient Population: New Data on the Genetic Background and Validation of the Fatigue Impact Scale
Témavezető neveBeosztás, tudományos fokozat, intézményEmail
Dr. Bencsik Krisztinaegyetemi docens, SZTE Neurológiai
EPrint azonosító (ID): 758
Publikációban használt név : MD Losonczi Erika
doi: 10.14232/phd.758
A feltöltés ideje: 2011. máj. 13. 14:09
Utolsó módosítás: 2014. szept. 02. 14:35
Egyebek (raktári szám): B 4895
Védés állapota: védett

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