Familial seropositive rheumatoid arthritis in North American Native families: effects of shared epitope and cytokine genotypes.
OBJECTIVE
A number of North American native (NAN) populations have high prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE). We examined the phenotype and familial incidence of RA in a NAN population, and investigated how the SE and cytokine genes may affect disease risk within affected families.


METHODS
NAN patients with seropositive RA or polyarthritis rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were identified from clinical databases. Patients were recruited consecutively as they presented for clinic visits. Family pedigrees were constructed and consenting relatives were interviewed and examined. The risk of RA within families was calculated by multiple logistic regression. Input variables were the SE and cytokine genotypes. Probands and affected relatives were entered as the affected group, and unaffected relatives within families as the unaffected group. Results were confirmed among unrelated subjects, i.e., unrelated patients and unaffected relatives of other probands.


RESULTS
The familial prevalence of RA was 0.50 (95% confidence intervals 0.30, 0.70) among 28 families studied. The interleukin 10 (IL-10) promoter -1082 G/A genotype decreased the odds of RA relative to the A/A genotype in affected families (OR 0.247, 95% CI 0.081, 0.751; p = 0.014) and among unrelated subjects (OR 0.203, 95% CI 0.064, 0.640; p = 0.006). The G/G genotype yielded an OR of 0.093 (95% 0.013, 0.676; p = 0.019) among unrelated subjects. The SE had no effect in these calculations.


CONCLUSIONS
There was a high familial prevalence of RA in this NAN cohort. In susceptible NAN families, the risk of RA was reduced by IL-10 genotypes, whereas the SE did not affect risk. Study of healthy NAN controls is required to determine if these conclusions apply to this NAN population as a whole.
Oen
Kiem
K
Department of Paediatrics and Child health; and the School of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. koen@exchange.hsc.mb.ca
Robinson
David B
DB
Nickerson
Peter
P
Katz
Steven J
SJ
Cheang
Mary
M
Peschken
Christine A
CA
Canvin
Janice M G
JM
Hitchon
Carol A
CA
Schroeder
Marial-Louise
ML
El-Gabalawy
Hani S
HS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012217:Rheumatoid Factor / Q000097:blood
D000939:Epitopes; D016753:Interleukin-10; D012217:Rheumatoid Factor