Genetic polymorphisms of rs73620203 in the transforming growth interacting factor gene associated with rheumatoid arthritis in a Chinese population.

• The rs73620203 locus is correlated with RA susceptibility, and the genotypes carrying the T allele are protective factors of RA. The same findings were illustrated in female RA patients. • Among the three genotypes CC, CT, and TT of rs73620203, serum osteocalcin and BALP levels were significantly lower in the TT genotype than in the CC and CT genotypes, while serum β-CTX levels were not significantly different. • It is inferred that T allele at rs73620203 in TGIF gene may be related to the role of the rs73620203 locus in regulating the TGIF gene expression and thus regulating the function of the Smad signaling pathway. • It is suggested that TGIF gene polymorphisms perhaps can be regarded as novel markers for predicting the risk of developing RA. To explore the association of single nucleotide polymorphisms (SNPs) in the transforming growth interacting factor (TGIF) gene with bone metabolism markers and rheumatoid arthritis (RA) susceptibility. Three SNPs were genotyped in 155 RA patients and 168 healthy controls using high-resolution melting (HRM) analysis. The serum levels of osteocalcin, bone alkaline phosphatase (BALP), and β type I collagen-crosslinked C telopeptide (β-CTX) were detected using electrochemical luminescence in 108 patients randomly selected from the RA group. Genotype and allele frequency analysis showed that rs73620203 was associated with bone erosion in RA (P = 0.012 and P = 0.003, respectively), and individuals carrying the T allele for rs73620203 showed a decreased RA risk (OR = 0.59, 95% CI = 0.42–0.84; P = 0.003). In sex-specific analysis, the rs73620203 polymorphism was associated with susceptibility to RA in women (P = 0.022 and P = 0.006, respectively). In addition, RA patients with three genotypes at the rs73620203 locus showed significant differences in serum osteocalcin and BALP (P = 0.006 and P = 0.037, respectively). Haplotype analysis revealed that the haploid ATG and GCA frequencies were significantly lower in the RA group (P = 0.036, OR = 0.693; P = 0.002, OR = 0.189, respectively), while the haploid ACA frequency of the RA group was enhanced (P < 0.01, OR = 5.058). Our study provides the first evidence that rs73620203 is associated with RA susceptibility and the relationship between TGIF gene SNPs and the regulation of bone metabolism in RA patients. [ABSTRACT FROM AUTHOR]