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A single nucleotide polymorphism in the MerTK gene is associated with increased radiological disease activity in
Melissa Minhui Chu1, Vivien Li1, Tomas Kalincik2
1Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Parkville VIC 3050, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville VIC 3052, Australia.
Background:
Mer tyrosine kinase (MERTK), is a regulator of immune activity. HLA-DRB1*1501 and MERTK are modulators of MERTK expression on monocytes, and risk genes for Multiple Sclerosis (MS). Natalizumab treatment inhibits lymphocyte but not monocyte ingress into the CNS.
Objective:
To examine the effect of MERTK modulating genes HLA-DRB1*1501 and MerTK SNP rs7422195 on non-lymphocytic immune activity in MS.
Methods:
A retrospective study was conducted at the Neuroimmunology Service, Royal Melbourne Hospital between December 2020 - May 2022. Patients with MS treated with natalizumab were included. Venous blood was collected for genotyping. Medical records and imaging were reviewed for assessment of disease activity. Rate ratios for clinical and radiological disease activity were modelled using negative binomial regression, weighted by follow up time.
Results:
No difference in relapse rate was observed in HLA-DRB1*1501 (+) vs (-) (RR 0.79 [0.31-2.0]; p = 0.63) or MerTK rs7422195 SNP GA/AA vs GG (RR 1.1 [0.38-3.4]; p = 0.81) groups. MerTK rs7422195 SNP GA/AA genotype but not HLA-DRB1*1501 (+) was associated with an increase in radiological disease activity (RR 18.7 [2.7 - 203.1]; p = 0.0030 and RR 2.4 [0.31-28.5]; p = 0.31, respectively).
Conclusion:
MerTK rs7422195 SNP GA/AA is associated with a higher rate of radiological disease activity in MS treated with natalizumab.
