Contributions
Abstract: EP1572
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 24 Neuropsychology
Background: Cognitive impairment is a common feature of multiple sclerosis (MS). There are still disputable questions about its morphological substrate and causation. The type and degree of cognitive dysfunction is not highly associated with disease course and physical disability, which emphasizes the need of disclosing the factors that determine the development of cognitive deficit.
Objective: The objectives of this study is to investigate the relationship between promoter polymorphisms -308A/G TNF-alpha, -1082A/G IL10 and -607C/A IL-18 and cognitive functioning in patients with relapsing-remitting MS (RRMS).
Methods: The study comprised 159 patients with RRMS, diagnosed according to McDonald's criteria (2010) in remission phase (mean age 40.08±8.48years, mean disease duration 10.60±5.70years) and 154 healthy controls matching by age, gender and education. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT) and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, verbal fluency and executive functions. Genotyping of the promoter polymorphisms in IL-10 and IL-18 was performed using ARMS-PCR assay, while polymorphism in TNF-alpha was genotyped by RFLP-PCR assay.
Results: Patients had lower mean score on all three neuropsychological tests than the controls (p< 0.0001). In the patients' group the following significant associations were found: AG genotype of -308A/G TNF-alpha was associated with higher serum TNF-alpha concentration than GG genotype (p=0.04), higher serum TNF-alpha levels correlated with poorer attention and visuo-perceptual abilities (SDMT) (p=0.033); CC genotype of -607C/A IL-18 was related to lower score on the test for verbal fluency and executive functions (Isaacs test) as compared to AC variant (p=0.04).
The test result was considered abnormal when the patient scored 2 standard deviations below the average performance of the control group. Carriers of AA genotype of -1082A/G IL-10 from the patients' group showed significantly higher risk for abnormally low performance on PASAT than GG carriers (OR=10.0; p=0.0471).
Conclusion: The results of our study suggest that cytokine gene polymorphisms are one of the factors that affect cognitive functions in patients with RRMS. In Bulgarian population two promoter polymorphisms in pro-inflammatory cytokine genes - IL-18 and TNF-alpha, are associated with cognitive decline in RRMS patients.
Disclosure: The study was funded by Medical University of Plovdiv as an university research project - grant # HO-02/2014.
Dr. A. Trenova: nothing to disclose
Dr. G. Slavov: nothing to disclose
Prof. M. Manova: nothing to disclose
Prof. Z. Zahariev: nothing to disclose
Assoc. prof. L. Miteva: nothing to disclose
Prof. S. Stanilova: nothing to disclose
Abstract: EP1572
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 24 Neuropsychology
Background: Cognitive impairment is a common feature of multiple sclerosis (MS). There are still disputable questions about its morphological substrate and causation. The type and degree of cognitive dysfunction is not highly associated with disease course and physical disability, which emphasizes the need of disclosing the factors that determine the development of cognitive deficit.
Objective: The objectives of this study is to investigate the relationship between promoter polymorphisms -308A/G TNF-alpha, -1082A/G IL10 and -607C/A IL-18 and cognitive functioning in patients with relapsing-remitting MS (RRMS).
Methods: The study comprised 159 patients with RRMS, diagnosed according to McDonald's criteria (2010) in remission phase (mean age 40.08±8.48years, mean disease duration 10.60±5.70years) and 154 healthy controls matching by age, gender and education. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT) and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, verbal fluency and executive functions. Genotyping of the promoter polymorphisms in IL-10 and IL-18 was performed using ARMS-PCR assay, while polymorphism in TNF-alpha was genotyped by RFLP-PCR assay.
Results: Patients had lower mean score on all three neuropsychological tests than the controls (p< 0.0001). In the patients' group the following significant associations were found: AG genotype of -308A/G TNF-alpha was associated with higher serum TNF-alpha concentration than GG genotype (p=0.04), higher serum TNF-alpha levels correlated with poorer attention and visuo-perceptual abilities (SDMT) (p=0.033); CC genotype of -607C/A IL-18 was related to lower score on the test for verbal fluency and executive functions (Isaacs test) as compared to AC variant (p=0.04).
The test result was considered abnormal when the patient scored 2 standard deviations below the average performance of the control group. Carriers of AA genotype of -1082A/G IL-10 from the patients' group showed significantly higher risk for abnormally low performance on PASAT than GG carriers (OR=10.0; p=0.0471).
Conclusion: The results of our study suggest that cytokine gene polymorphisms are one of the factors that affect cognitive functions in patients with RRMS. In Bulgarian population two promoter polymorphisms in pro-inflammatory cytokine genes - IL-18 and TNF-alpha, are associated with cognitive decline in RRMS patients.
Disclosure: The study was funded by Medical University of Plovdiv as an university research project - grant # HO-02/2014.
Dr. A. Trenova: nothing to disclose
Dr. G. Slavov: nothing to disclose
Prof. M. Manova: nothing to disclose
Prof. Z. Zahariev: nothing to disclose
Assoc. prof. L. Miteva: nothing to disclose
Prof. S. Stanilova: nothing to disclose