Genetic variation and significant association of polymorphism rs7700944 G>A of TIM-4 gene with rheumatoid arthritis susceptibility in Chinese Han and Hui populations

The T-cell immunoglobulin and mucin domains 1 (TIM-1) and 3 (TIM-3) have been shown to be associated with susceptibility to rheumatoid arthritis (RA) in many ethnicities. In this study, we investigated the rs7700944 polymorphism of the intron region of TIM-4 gene in Chinese Han and Hui populations, with and without RA in Ningxia Hui Autonomous Region of China. Our results demonstrated genetic variations of the TIM-4 gene, along with significantly different distributions of genotypes and alleles at rs7700944 site in these two populations, with or without RA (P < 0.01). In addition, a strong association between the polymorphism with RA susceptibility was found in the studies of Chinese Han and Hui ethnic groups (P < 0.01), although the risk genotype contributed to RA susceptibility was different between the Han and Hui groups (P < 0.01). The AG was the risk genotype for RA in Han population, while GG was the risk genotype at rs7700944 site of TIM-4 gene in Hui ethnicity. In addition to the genotype, the risk alleles of this single nucleotide polymorphism for RA in these two populations were also different, individuals with A allele was more susceptible to RA in Chinese Han [odds ratio (OR) = 1.930; 95% CI 1.412, 2.636; P < 0.01], but the risk allele in Hui was G in this study (OR = 1.823; 95% CI 1.330, 2.498; P < 0.01). These findings strongly suggest that polymorphism of rs7700944 of TIM-4 may be a potential genetic variant among distinguished populations, as well as an important genetic factor associated with the RA susceptibility in many ethnicities.