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Liver kinase B1 rs9282860 polymorphism and risk for multiple sclerosis in White and Black Americans

Published:August 02, 2021DOI:https://doi.org/10.1016/j.msard.2021.103185

      Highlights

      • A SNP risk factor for MS in the STK11 gene is present at higher frequency in African American compared to White MS patients.
      • The SNP is present at higher frequency in SPMS patients than RRMS or control subjects.
      • In SPMS patients, the SNP is associated with older age at onset and at diagnosis.
      • The STK11 SNP may represent a biomarker for conversion from RRMS to SPMS.

      Abstract

      Background

      We previously reported that the single nucleotide polymorphism (SNP) rs9282860 in serine threonine kinase 11 (STK11) gene which codes for liver kinase B1 (LKB1) has higher prevalence in White relapsing-remitting multiple sclerosis (RRMS) patients than controls. However it is not known if this SNP is a risk factor for MS in other populations.

      Methods

      We assessed the prevalence of the STK11 SNP in samples collected from African American (AA) persons with MS (PwMS) and controls at multiple Veterans Affairs (VA) Medical Centers and from a network of academic MS centers. Genotyping was carried out using a specific Taqman assay. Comparisons of SNP frequencies were made using Fisher's exact test to determine significance and odds ratios. Group means were compared by appropriate t-tests based on normality and variance using SPSS V27.

      Results

      There were no significant differences in average age at first symptom onset, age at diagnosis, disease duration, or disease severity between RRMS patients recruited from VAMCs versus non-VAMCs. The SNP was more prevalent in AA than White PwMS, however only in secondary progressive MS (SPMS) patients was that difference statistically significant. AA SPMS patients had higher STK11 SNP prevalence than controls; and in that cohort the SNP was associated with older age at symptom onset and at diagnosis.

      Conclusions

      The results suggest that the STK11 SNP represents a risk factor for SPMS in AA patients, and can influence both early (onset) and later (conversion to SPMSS) events.

      Keywords

      Abbreviations:

      AA (African American), CIS (Clinically isolated syndrome), EAE (Experimental autoimmune encephalomyelitis), EDSS (Expanded disability severity score), gDNA (Genomic DNA), GWAS (Genome wide array study), LKB1 (Liver kinase B1), MHC (Major histocompatibility complex), MSSR (MS Surveillance Registry), MSSS (MS severity score), mtDNA (Mitochondrial DNA), OR (Odds Ratio), PPMS (Primary progressive MS), PwMS (Patients with MS), RRMS (Relapsing-remitting MS), SNP (Single nucleotide polymorphism), SPMS (Secondary progressive MS), STK11 (Serine threonine kinase 11), VALOMS (Veterans Affairs Longitudinal MS Study), VAMC (Veterans Affairs Medical Center)
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