BACKGROUND:More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown.
OBJECTIVE: The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation.
METHODS: A cumulative genetic risk score was based on four human leucocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric analyses were applied.
RESULTS: An increased genetic risk is observed for MS patients, including subsets such as oligoclonal band-negative and primary progressive MS patients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset.
CONCLUSION: MS patients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MS patients, the HLA region influences intrathecal IgG levels.
The more risk factors you have the more at risk you are.
Lulu S, Graves J, Waubant E. Menarche increases relapse risk in pediatric multiple sclerosis. Mult Scler. 2015 May 6. pii: 1352458515581873. [Epub ahead of print]
BACKGROUND:Multiple sclerosis (MS) predominantly affects women with a sex ratio of 3:1 in contrast with a 1:1 sex ratio seen in pre-pubertal onset. Thus, puberty may influence MS risk differentially in males and females. How puberty may be associated with MS clinical features and disease course remains unknown.
OBJECTIVE:The objective of this paper is to determine the association of menarche with disease course in girls with MS.
METHODS:This is a longitudinal retrospective study from the UCSF Regional Pediatric MS Center database. We categorized patients by time of disease onset: pre-menarche, peri-menarche and post-menarche.
RESULTS:Seventy-six girls were included (pre-menarche onset = 17; peri-menarche onset = 9; post-menarche onset = 50). Age of menarche was similar in all groups Relapse rate was the same in all three groups during the first two years of follow-up. In girls with follow-up overlapping at least two time periods, within-subject analyses showed increased relapses during the peri-menarche compared to post-menarche period (adjusted IRR = 8.5, 95% CI 2.5-28.7, p = 0.001).
CONCLUSION: Pubertal status may influence MS course at least in female patients. Understanding how puberty influences MS clinical features may offer new insights into important factors regulating disease processes.
Lulu S, Graves J, Waubant E. Menarche increases relapse risk in pediatric multiple sclerosis. Mult Scler. 2015 May 6. pii: 1352458515581873. [Epub ahead of print]
BACKGROUND:Multiple sclerosis (MS) predominantly affects women with a sex ratio of 3:1 in contrast with a 1:1 sex ratio seen in pre-pubertal onset. Thus, puberty may influence MS risk differentially in males and females. How puberty may be associated with MS clinical features and disease course remains unknown.
OBJECTIVE:The objective of this paper is to determine the association of menarche with disease course in girls with MS.
METHODS:This is a longitudinal retrospective study from the UCSF Regional Pediatric MS Center database. We categorized patients by time of disease onset: pre-menarche, peri-menarche and post-menarche.
RESULTS:Seventy-six girls were included (pre-menarche onset = 17; peri-menarche onset = 9; post-menarche onset = 50). Age of menarche was similar in all groups Relapse rate was the same in all three groups during the first two years of follow-up. In girls with follow-up overlapping at least two time periods, within-subject analyses showed increased relapses during the peri-menarche compared to post-menarche period (adjusted IRR = 8.5, 95% CI 2.5-28.7, p = 0.001).
CONCLUSION: Pubertal status may influence MS course at least in female patients. Understanding how puberty influences MS clinical features may offer new insights into important factors regulating disease processes.