Abstract
We conducted a comparative analysis of clinical and demographic findings between pairs
of relatives (36 sibling and 9 parent/child), concordant for Multiple Sclerosis (MS),
from 40 MS Italian Multiplex families. A genetic TNF (α and β) loci typing in 51 affected
and 69 healthy relatives belonging to 25 of these families was also performed. The
sib pairs resulted significantly concordant for age at onset (r=0.414, P<0.013), Progression Index (r=0.34, P<0.05) and sensory symptoms at onset (k=0.37), and significantly not concordant for sex (k=−0.37), whereas no concordance was found for year at onset and disease course. The
only significant result in the small group of parent/child pairs was that parents
developed MS at an age of 18.74 years significantly (P=0.020) greater than their children. Genomic analysis identified 13 variants of TNF-a
alleles, 7 of TNF-b, 6 of TNF-d and 3 of TNF-e. No differences in the frequencies
of the various TNF alleles were observed between affected and healthy relatives. The
two-point lod-score analysis of the TNF locus showed not significant or negative results
for the TNFα loci and slightly positive results (Zmax=0.4 at θ=0.2 cM) for the TNFβ-b locus in the lowest penetrance dominant model. The Sib pair
analysis, using combined TNFα and TNFβ haplotypes, demonstrated a TNF allele sharing
between affected sib-pairs which did not exceed the expected 50%. These results suggest
that genetic factors may partially influence the disease onset and the progression
rate in sibling pairs. A recall bias and/or an ‘anticipation phenomenon’ could explain
the development of MS at an older age in parents than in their children. In this small-sized
cohort of MS Italian families no significant associations were confirmed between TNF
polymorphism and MS.
Keywords
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Article info
Publication history
Accepted:
December 8,
1998
Received in revised form:
October 12,
1998
Received:
February 27,
1998
Identification
Copyright
© 1999 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
