Association of APOE polymorphisms with disease severity in MS is limited to women
JackZwemmer, Dept. of Neurology, VU Medical Center, Postbox 7057, 1007 MB Amsterdam, The Netherlandsjnp.zwemmer@vumc.nl
Bernard Uitdehaag, Gerard van Kamp, Frederik Barkhof, Chris Polman
Submitted April 06, 2004
We read the article by Kantarci et al with great interest. It examined the
gender specific association of APOE polymorphisms with disease severity in
MS.[1] Gender specificity is important and has not been previously addressed. We recently analyzed and
described APOE polymorphisms in relation to MS susceptibility, disease
characteristics (including age at onset and onset type), disease severity
(progression index, time to reach EDSS 6) and MRI findings (lesion volumes
and atrophy measures) in a cohort of 408 MS patients, but did not focus on
gender specificity.[2]
In an attempt to validate the findings by Kantarci
et al, we re-analyzed our data applying similar methods.
Our cohort included 250 women and 158 men, mean age at onset (± SD) 32.3 ±
9.5 years, mean disease duration 13.4 ± 8.0 years, median time to EDSS 6
9.2 (IQR 5.4 - 14.0) years, and 39% RR, 39% SP and 22% PP.
Genotype and carrier frequencies were not significantly different between genders but they did contain a smaller percentage of epsilon 2 carriers (16.4%)
compared to the cohort of Kantarci et al and the absolute number was larger.
After stratification for gender, no favorable role for epsilon 2
carriership was found in women. In fact, a trend in the opposite direction
was found: time to EDSS 6 in women was shorter in epsilon 2 carriers than
in non-carriers (median (IQR): 6.8 (3.7 - 9.3) vs. 10.0 (5.8 - 12.9)
years, p=0.10). This unfavorable association of epsilon 2 carriership was
supported by MRI measures in partially overlapping subgroups for which
repeated T2 (n=174) and T1 lesion loads (n=109) were available. Compared
to non-carriers, female epsilon 2 carriers had a significantly higher
relative increase in T2 (p=0.02) and T1 (p=0.03) lesion loads (linear
regression with correction for age, onset type, disease duration and IFN-
therapy). In men, no significant differences were found between epsilon 2
carriers and non-carriers.
In conclusion, we were unable to confirm the findings by Kantarci et
al that in women epsilon 2 carriership is associated with a more
favorable disease course. In contrast, by applying likewise analysis we
found a trend in the opposite direction. The findings from these two
studies can be added to an increasing pool of controversial results
regarding the association of APOE polymorphisms and MS. Larger studies
or meta-analyses of existing data are necessary and caution should be
taken when interpreting results regarding the association of the APOE
polymorphism and MS, also with respect to gender specificity.
References
1. Kantarci OH, Hebrink DD, Achenbach SJ, et al. Association of APOE
polymorphisms with disease severity in MS is limited to women. Neurology
2004;62:811-814.
2. Zwemmer JNP, van Veen T, van Winsen L, et al. No major association
of ApoE genotype with disease characteristics and MRI findings in multiple
sclerosis. Mult Scler 2004; in press.
We read the article by Kantarci et al with great interest. It examined the gender specific association of APOE polymorphisms with disease severity in MS.[1] Gender specificity is important and has not been previously addressed. We recently analyzed and described APOE polymorphisms in relation to MS susceptibility, disease characteristics (including age at onset and onset type), disease severity (progression index, time to reach EDSS 6) and MRI findings (lesion volumes and atrophy measures) in a cohort of 408 MS patients, but did not focus on gender specificity.[2]
In an attempt to validate the findings by Kantarci et al, we re-analyzed our data applying similar methods. Our cohort included 250 women and 158 men, mean age at onset (± SD) 32.3 ± 9.5 years, mean disease duration 13.4 ± 8.0 years, median time to EDSS 6 9.2 (IQR 5.4 - 14.0) years, and 39% RR, 39% SP and 22% PP. Genotype and carrier frequencies were not significantly different between genders but they did contain a smaller percentage of epsilon 2 carriers (16.4%) compared to the cohort of Kantarci et al and the absolute number was larger.
After stratification for gender, no favorable role for epsilon 2 carriership was found in women. In fact, a trend in the opposite direction was found: time to EDSS 6 in women was shorter in epsilon 2 carriers than in non-carriers (median (IQR): 6.8 (3.7 - 9.3) vs. 10.0 (5.8 - 12.9) years, p=0.10). This unfavorable association of epsilon 2 carriership was supported by MRI measures in partially overlapping subgroups for which repeated T2 (n=174) and T1 lesion loads (n=109) were available. Compared to non-carriers, female epsilon 2 carriers had a significantly higher relative increase in T2 (p=0.02) and T1 (p=0.03) lesion loads (linear regression with correction for age, onset type, disease duration and IFN- therapy). In men, no significant differences were found between epsilon 2 carriers and non-carriers.
In conclusion, we were unable to confirm the findings by Kantarci et al that in women epsilon 2 carriership is associated with a more favorable disease course. In contrast, by applying likewise analysis we found a trend in the opposite direction. The findings from these two studies can be added to an increasing pool of controversial results regarding the association of APOE polymorphisms and MS. Larger studies or meta-analyses of existing data are necessary and caution should be taken when interpreting results regarding the association of the APOE polymorphism and MS, also with respect to gender specificity.
References
1. Kantarci OH, Hebrink DD, Achenbach SJ, et al. Association of APOE polymorphisms with disease severity in MS is limited to women. Neurology 2004;62:811-814.
2. Zwemmer JNP, van Veen T, van Winsen L, et al. No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis. Mult Scler 2004; in press.