This study attempts to identify the genes responsible for rheumatoid arthritis (RA), or
inflammation of the joints. It is known that genes play an important role in RA, but their
number and significance have not been determined. RA tends to run in families. This study
will examine the DNA (hereditary material) of patients with RA and their family members to
try to determine which chromosomes(s) contain the genes responsible for the disease.
Patients with rheumatoid arthritis and their family members may be eligible for this study.
Participants with RA who have a brother or sister with RA will undergo the following
- Review of their medical records
- Medical history
- Examination of the joints
- Hand X-rays
- Blood tests
Participants who 1) do not have RA but who have a relative with the disease, or 2) have RA
and a relative other than a brother or sister who has the disease will provide a blood
sample or a buccal (cheek) cell sample. Cheek cells are obtained by swishing a small amount
of mouthwash in the mouth or by lightly bushing the inside of the cheek with a swab or
The samples will be tested for rheumatoid factor, DNA studies, and HLA type (a blood type
found on white blood cells). Certain HLA types have been associated with an increased risk
or severity of RA.
The purpose of this protocol is to identify genetic susceptibility loci for rheumatoid
arthritis. The Genetics and Genomics Branch of the Intramural Research Program of NIAMS [now
Inflammatory Diseases Section of the Intramural Research Program of NHGRI] has joined with
several extramural centers to form the North American Rheumatoid Arthritis Consortium
(NARAC). The Consortium intends to identify and obtain clinical specimens on a total of 1000
sibling pairs with rheumatoid arthritis; up to 100 sibling pairs will be recruited at the
Center. Samples from parents and other family members will also be obtained, where
appropriate. Rheumatoid factors, HLA-DR typings, and hand films will be obtained on all
sibling pairs. In addition, DNA will be extracted from peripheral blood or buccal scrapings.
DNA from all 1000 sibling pairs will be typed for a set of approximately 350 genetic markers
order to identify chromosomal regions likely to harbor genes conferring susceptibility to
rheumatoid arthritis. For those chromosomal regions that are positive in this initial
families will be genotyped for additional markers to define disease-associated haplotypes,
and high density single nucleotide polymorphism (SNP) analysis will be conducted to narrow
the regions of interest. Candidate genes will be chosen from the narrowed regions of
interest, and/or based on functional considerations, and will be screened for mutations in
- INCLUSION CRITERIA:
A diagnosis of rheumatoid arthritis in both sibs by the 1987 ACR criteria.
Definite bony erosions in at least one affected sibling.
Age of disease onset greater than 18 years and less than 60 years in at least one sibling.
Neither sibling has psoriasis, inflammatory bowel disease, or systemic lupus
BLOOD RELATIVES OF AFFECTED SIBLING PAIRS:
Age greater than 18 years.
Where possible, all other affected siblings will be invited to participate.
Where possible, both parents of affected siblings will be invited to participate.
Other relatives, both affected and unaffected, may be invited to participate if, in the
opinion of the investigators, samples from these individuals would contribute important
genetic information. Two cases in which this might happen are: a) extended families in
which there are several affected individuals, where conventional linkage analysis might be
applied; b) affected sibling pairs for which parents are unavailable, where additional
siblings will provide information on parental alleles not transmitted to the affected
EXCLUSION CRITERIA FOR AFFECTED SIBLINGS:
Psoriasis, inflammatory bowel disease, systemic lupus erythematosus.
Inability to provide infomed consent.
The sole criterion for exclusion of adult blood relatives of affected sibling pairs would
be inability to provide informed consent.