Influence of APOE gene polymorphisms on interferon-beta treatment response in multiple sclerosis

Clinical trials with interferon beta in relapsing remitting multiple sclerosis (RRMS) have demonstrated a reduction in the relapse rate. Nevertheless, not all patients respond to this treatment, although there is no consensus regarding the definition of response to therapy. The reasons for this failure are not known but genetic factors probably influence this, as has been previously shown with Interleukin 10 or Interferon gamma polymorphisms. The role of apolipoprotein E (APOE) gene in MS has been investigated and does not appear to increase risk for MS or influence disease severity. Interestingly APOE variation influences response to cholinesterase inhibitor treatment in Alzheimer disease or to statins in hypercholesterolemia. This might have future implications for MS.

We retrospectively reviewed 38 RRMS patients (32 females and 6 males) treated with interferon beta (INFbeta) over at least two years. Criteria for treatment were uniform accordingly to an "Advisory Committee for the Treatment of Multiple Sclerosis". We collected data variables including age, age of onset, clinical type or disease duration. Patients were classified, two years after the start of treatment, as responders and non-responders based upon clinical criteria available in the literature, which rely on the presence of relapses, increase of disability, or both. APOE genotype was determined from blood samples using validated polymerase chain reaction methods. Correlation between patient responding status with allele E2 or E4 was tested.

A total of 20 patients (52.6%) received subcutaneous INFbeta1b (Betaferón(®)), 13 (34.2%) INFbeta1a intramuscular (Avonex(®)), and 5 (13.2%) subcutaneous INFbeta1a (Rebif(®)). We found 2 patients (5.2%) heterozygous for the E2 allele and 9 (23.7%) for the E4 allele. No patient was homozygous for E2 or E4. Comparison of patients with and without E2 or E4 allele showed no significant differences in any of the ten therapy response variables assessed.

Findings of a recent meta-analysis have not supported a role for APOE in MS susceptibility or severity. We have not found, in our data, any influence of this gene in the RRMS response to INFbeta. However, larger series would be required to validate these results.