TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population |
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| Authors: | Juraj Javor Ivana Shawkatová Vladimíra Ďurmanová Zuzana Párnická Daniel Čierny Jozef Michalik Daniela Čopíková‐Cudráková Barbora Smahová Karin Gmitterová Ľubica Peterajová Mária Bucová |
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| Affiliation: | 1. Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia;2. Department of Clinical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava and University Hospital Martin, Martin, Slovakia;3. Clinic of Neurology, Jessenius Faculty of Medicine, Comenius University in Bratislava and University Hospital Martin, Martin, Slovakia;4. 1st Department of Neurology, Faculty of Medicine, Comenius University in Bratislava and University Hospital Bratislava, Bratislava, Slovakia;5. 2nd Department of Neurology, Faculty of Medicine, Comenius University in Bratislava and University Hospital Bratislava, Bratislava, Slovakia;6. Haematology Outpatient Clinic, University Hospital Bratislava, Bratislava, Slovakia |
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| Abstract: | Tumour necrosis factor (TNF)‐mediated signalling plays a key role in inflammatory and neurodegenerative processes leading to the development of multiple sclerosis (MS). Recent studies have highlighted the role of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) gene encoding the type 1 TNF receptor in the genetic predisposition to MS. This study aimed to validate the association of TNFRSF1A rs1800693 and rs4149584 polymorphisms with susceptibility to MS in the Slovak population and analyse their influence on age at disease onset, severity, and disability progression. Polymerase chain reaction–restriction fragment length polymorphism method was used to genotype both TNFRSF1A polymorphisms in 541 MS patients and 724 healthy controls. Logistic regression analysis revealed a significantly increased risk of developing MS for the carriers of rs1800693 C allele (TC + CC vs. TT: pcorr = 0.005; OR = 1.61; 95% CI = 1.23–2.12), irrespective of sex and carriage of the major MS risk allele HLA‐DRB1*15:01. On the other hand, no association could be found between rs4149584 and MS risk (GA + AA vs. GG: pcorr = 1.00; OR = 1.25; 95% CI = 0.71–2.21). Moreover, neither polymorphism was significantly associated with age at disease onset, MS Severity Score (MSSS) or MS Progression Index (PI) in any of the inheritance models. In conclusion, our results provide support for a sex‐ and HLA‐DRB1*15:01‐independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation. |
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| Keywords: | multiple sclerosis polymorphism severity susceptibility TNFRSF1A |
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