Polymorphisms in () are Linked to Infection and Osteoporosis in Rheumatoid Arthritis.

We previously discovered that single nucleotide polymorphisms (SNPs) in (T-cell negative-regulators) occur in 78% of rheumatoid arthritis (RA), along with (MAP) infection in 33% of patients. In Crohn's disease, we reported that SNPs in and receptors () benefited intracellular MAP-survival, increased infection, and elevated inflammatory response mimicking the poor response to anti-TNF treatment in some patients. Here, we studied the frequency and effects of SNPs in in RA including gene expression, MAP infection, and osteoporosis marker levels in blood (54 RA and 48 healthy controls). (GA) was detected in 19/48 (40%) RA and 8/54 (15%) controls (-value < 0.05, odds ratio (OR) = 3.6, 95% CI: 1.37-9.54). (CT) was detected in 21/48 (44%) RA and 10/54 (19%) controls (-value < 0.05, OR = 4.43, 95% CI: 1.73-11.33). In RA, downregulated expression (CC > CT (0.34 ± 0.14) and CC > TT (0.27 ± 0.12)), compared to wildtype CC (0.51 ± 0.17), -value < 0.05. MAP DNA was detected significantly in 17/48 (35.4%) RA compared to 11/54 (20.4%) controls (-value < 0.05, OR = 2.14, 95% CI: 1.12-5.20). The average osteocalcin level was significantly lower (-value < 0.05) in RA (2.70 ± 0.87 ng/mL), RA + MAP (0.60 ± 0.31 ng/mL), RA + (TT) (0.67 ± 0.35 ng/mL), compared to the healthy control (5.31 ± 1.39 ng/mL), and MAP-free RA (3.85 ± 1.31 ng/mL). Overall, appears to downregulate , increase MAP infection, worsen inflammation, and cause osteocalcin deficiency and possibly osteoporosis in RA.