Subgroups in Fibromyalgia
Aspects of Fibromyalgia Syndrome
B. Yunus, M.D.
University of Illinois College of Medicine at Peoria, Peoria, Illinois
Genetic factors in fibromyalgia
syndrome (FMS) have been suspected because of familial clustering of this
disorder. Pellegrino, et al had studied 17 patients with FMS from a support
group and their 50 parents and siblings and found that 52% of these relatives
had FMS (Arch Phys Med Rehabil 1989; 70:61-63); they also concluded that
FMS is an autosomal dominant disease. Buskila, et al investigated 30 FMS
patients and 91 of their first-degree relatives (FDR) and reported that
26% of the FDR had FMS (J Rheumatol 1997; 24:941-44). Rosenblatt et al
diagnosed FMS among 71% mothers of 34 children with FMS (J Musculoskel
Pain 1995; 2 (suppl 1): 118). However these reports of familial aggregation
do not confirm role of genetics in FMS because of the influence of environmental
factors in such aggregation.
Studies of an association between
FMS and an HLA allele are inclusive. Burda, et al studied only 18 patients
with FMS and 23 normal controls and found a significant association with
DR4 (Clin Exp Rheumatol 1986; 4:355-7). Branco, et al investigated 52
FMS patients and 869 normal controls and found an association of HLA B58,
DR8 and DR5 (J Musculoskel Pain 1996; 4:21-7). However, Horven et al,
in an earlier report, found no HLA association among 60 patients with
FMS and 159 normal controls (J Rheumatol 1992; 19:1269-70).
We investigated 40 multicase families
with FMS and sought to determine genetic linkage of FMS with HLA. Such
linkage studies avoid the biases involved in HLA association studied.
Eighty-five affected and 21 unaffected members of 41 sibships were studied
clinically and by HLA typing. We analyzed data by model-free linkage method
which examine identity-by-descent (IBD) sharing among sets of relatives
and do not require specification of the mode of inheritance. Sibship analysis
showed a weak (P=0.028) linkage of FMS to the HLA region.
In collaboration with the Case
Western Reserve University, Cleveland, we now plan to study an additional
120 families to confirm our earlier report, and importantly, to perform
a genome scan on the family members of our earlier 40 and new 120 (a total
of 160 families) for over 200 genetic markers at 20 cM intervals throughout
the genome. We will also include markers close to selected candidate genes,
e.g., serotonin transporter, tachykinin2 (substance P), IGF 1, growth
hormone and nerve growth factor beta-subunit. This and other genetic studies
in progress promise to provide exciting new information on the genetics
of fibromyalgia syndrome.
Presented at the National Fibromyalgia
Research Association's Subgroups in Fibromyalgia Symposium, September
26-27, 1999, in Portland, Oregon.