Myasthenia gravis (MG) is a rare autoimmune disease mediated by antibodies against
components of the neuromuscular junction, particularly the acetylcholine receptor
(AChR). The prevalence of MG in Belgrade has been estimated at 189 cases per
1,000,000 inhabitants, which is among the highest prevalence reported to date.
Genetic studies have mainly pointed to specific HLA alleles associated with MG.
However, CTLA-4 and TNFRSF11A, playing a role in the immune response, have
recently been associated with MG in genome-wide association studies. Since CTLA-4
and TNFRSF11A promote other autoimmune diseases, the main objective of this casecontrol
study was to determine the association between these candidate genes and the
risk for developing MG in Serbian population.
Genotyping of rs231735 and rs231770 within the CTLA-4 gene and rs4263037 within
TNFRSF11A in 447 AChR-MG patients and 447 individually sex- and age-matched
controls revealed no association with MG (p=0.344, p=0.923 and p=0.557,
respectively). However, when stratifying patients into those with early-onset (n=183)
and late-onset MG (n=264), we found an association of minor rs231735 allele T with
early-onset MG under the recessive genetic model (OR=0.548, 95% CI=0.339-0.888,
p=0.014, p10e6 permutation=0.014). Haplotype analysis revealed that individuals
with the GC haplotype rs231735-rs231770 had a higher risk for developing earlyonset
MG (OR =1.360, p=0.027, p10e6 permutation =0.027). Considering the
sufficient statistical power of the study (>90%) and the selection criteria for controls,
our results suggest that the CTLA-4 may be associated with early-onset MG in Serbian
population. Analysis of additional variants is needed to understand the association of
CTLA-4 with MGBOOK OF ABSTRACTS: 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international participation 31 May – 2 June 2023. Belgrade, Serbi
