JAK-STAT signaling pathway-related gene single nucleotide polymorphisms and susceptibility to ankylosing spondylitis in eastern Chinese Han population.

Objective: A case-control study was utilized to investigate the relationship between genetic variation of JAK-STAT signaling pathway-related genes and the susceptibility to ankylosing spondylitis (AS).

Methods: Fifteen SNPs in the JAK-STAT signaling pathway-related genes from 660 AS patients and 646 healthy controls were genotyped using iMLDR technology (JAK1: rs2230587, rs2230588, rs2780815, rs310241; JAK2: rs2274472, rs2230722, rs2230724, rs10758669; STAT1: rs10199181, rs1547550, rs2066802, rs45463799, rs6718902; STAT3: rs3744483; STAT5A: rs1135669).

Results: Allele analysis revealed that the T allele of STAT1 rs6718902 was a protective agent for male AS patients (OR = 0.765, 95% CI = 0.644-0.909). Inheritance models showed that GG + CG as well as GG genotypes of STAT1 rs1547550 had a significant risk of developing AS in males (OR = 5.374, 95%CI = 2.505-11.526; OR = 5.186, 95%CI = 2.412-11.153). The TT + CT and TT genotypes at STAT1 rs6718902 were observed to be associated with a significantly decreased risk of AS compared to CC genotypes among male patients and male controls (OR = 0.637, 95%CI = 0.485-0.837; OR = 0.597, 95%CI = 0.422-0.845). Furthermore, the genotypes of JAK1 gene rs2230588, rs2780815, and rs310241 were correlated with the severity of clinical conditions in female AS patients, while the JAK2 rs2230724 genotypes may affect disease ability in male AS patients.

Conclusion: These findings indicated that JAK-STAT signaling pathway-related gene single nucleotide polymorphisms may be associated with AS susceptibility in eastern Chinese Han population. Key Points • The T allele of rs6718902 on the STAT1 gene may be a protective agent for male AS patients. • STAT1 rs1547550 GG + CG and GG genotypes were observed to be connected with a risk of male AS patients. However, STAT1 rs6718902 TT + CT and TT genotypes reduced the susceptibility risk of male AS patients compared to wild-type CC. • The JAK1 genes rs2230588, rs2780815, and rs310241 may affect disease functional status in female AS patients, while the JAK2 rs2230724 genotype was related to disease activity in male AS patients.