Abstract:

Objective To study the association of four SNPs and haplotypes of Tim-1 gene with rheumatoid arthritis (RA) in Ningxia Hui population and provide theoretical basis early prevention of RA.Methods Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP),specific sequence primer-polymerase chain reaction (SSP-PCR) genotyping method were carried out to examine the －1637A>G,－1454 G>A，－416 G>C and －232 A>G polymorphic sites of Tim-1 gene,including 104 healthy individuals and 108 RA patients in Ningxia Hui population.Results The genotypic  frequencies at －1637,－232 sites and allelic frequency at －1637 site of Tim-1 gene had extremly significant difference (P<0.01) between RA patients and non-RA controls.The frequency of allele A in RA patients was significantly higher than that in non-RA controls (P<0.01) at －1637 site.The frequencies of the two haplotypes AGCA (OR 9.611,95%CI 3.13－29.52),and AGCG (OR 4.361,95%CI 2.12－8.96) in RA patients were higher than those in non-RA controls (P<0.01).The frequencies of the three haplotypes GGCA (OR 0.374，95%CI 0.22－0.64),GGCG (OR 0.199，95%CI 0.08－0.49) and GAGA (OR 0.023，95%CI 0.002－0.260) in RA patients were lower than those in non-RA controls (P<0.01).Conclusion －1637,－1454,－416,and －232 sites of Tim-1 gene have variations.－1637A>G polymorphisms of Tim-1 gene may be strongly associated with RA susceptibility in Ningxia Hui population.The haplotypes AGCA and AGCG  are  associated with RA.The haplotypes GGCA,GGCG,and GAGA have protective effects on  RA.

Key words: T cell immunoglobulin domain and mucin domain protein;rheumatoid arthritis;Ningxia Hui nationality;single nucleotide polymorphisms;haplotype