The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and selectively expressed on Th2 cells. In the present study, we analyzed the association of genotype and allele frequencies between rheumatoid arthritis (RA) patients and the controls without RA using large samples size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene. We further investigated the relationships among these variations to C-reactive protein (CRP) and rheumatoid factor (RF) levels in RA patients. Although these factors were not associated with exon 4 variations in RA patients, the genotype and allele frequencies of 5383_5397del variation site (P = 0.015 and 0.014, respectively) as well as 5509_5511delCAA variation site (P = 0.0002 and 0.0001, respectively) in RA patients were significantly different from those in the non-RA controls. Our results strongly suggest that the variations of Tim-1 exon 4 might be associated with the susceptibility to RA. (C) 2004 Elsevier Inc. All rights reserved.