Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Polymorphism rs2073618 of the TNFRSF11B (OPG) Gene and Bone Mineral Density in Mexican Women with Rheumatoid Arthritis.

Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in the TNFRSF11B osteoprotegerin (OPG) gene has been related to postmenopausal OP although, to date, no information has been described concerning whether this polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We evaluated, in a case-control study performed in Mexican-Mestizo women with RA, whether SNP rs2073618 in the TNFRSF11B gene is associated with a decrease in BMD. RA patients were classified as follows: (1) low BMD and (2) normal BMD. All patients were genotyped for the rs2073618 polymorphism by PCR-RFLP. The frequency of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal BMD (62 and 54 years, resp.; p < 0.001). Worse functioning and lower BMI were observed in RA with low BMD (p = 0.003 and p = 0.002, resp.). We found similar genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype 71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; p = 0.6). We concluded that in Mexican-Mestizo female patients with RA, the rs2073618 polymorphism of the TNRFS11B gene is not associated with low BMD.

Association between -174G/C and -572G/C interleukin 6 gene polymorphisms and severe radiographic damage to the hands of Mexican patients with rheumatoid arthritis: a preliminary report.

Several interleukin 6 gene (IL6) polymorphisms are implicated in susceptibility to rheumatoid arthritis (RA). It has not yet been established with certainty if these polymorphisms are associated with the severe radiographic damage observed in some RA patients, particularly those with the development of joint bone ankylosis (JBA). The objective of the present study was to evaluate the association between severe radiographic damage in hands and the -174G/C and -572G/C IL6 polymorphisms in Mexican Mestizo people with RA. Mestizo adults with RA and long disease duration (>5 years) were classified into two groups according to the radiographic damage in their hands: a) severe radiographic damage (JBA and/or joint bone subluxations) and b) mild or moderate radiographic damage. We compared the differences in genotype and allele frequencies of -174G/C and -572G/C IL6 polymorphisms (genotyped using polymerase chain reaction-restriction fragment length polymorphism) between these two groups. Our findings indicated that the -174G/C polymorphism of IL6 is associated with severe joint radiographic damage [maximum likelihood odds ratios (MLE_OR): 8.03; 95%CI 1.22-187.06; P = 0.03], whereas the -572G/C polymorphism of IL6 exhibited no such association (MLE_OR: 1.5; 95%CI 0.52-4.5; P = 0.44). Higher anti-cyclic citrullinated peptide antibody levels were associated with more severe joint radiographic damage (P = 0.04). We conclude that there is a relevant association between the -174G/C IL6 polymorphism and severe radiographic damage. Future studies in other populations are required to confirm our findings.

Association between bone turnover markers, clinical variables, spinal syndesmophytes and bone mineral density in Mexican patients with ankylosing spondylitis.

OBJECTIVES: To compare bone turnover marker (BTM) levels and bone mineral density (BMD) between patients with ankylosing spondylitis (AS) and healthy controls (HC) and to evaluate, in AS, the association between BTM levels and clinical variables, spinal syndesmophytes, and BMD using multivariate analysis. METHOD: Seventy-eight AS patients were compared with 58 HC matched by gender. Spinal syndesmophytes in AS and other characteristics were assessed. C-terminal telopeptide fragments of type I collagen (CTX), bone-specific alkaline phosphatase (BAP), osteocalcin (OC) serum levels, and BMD of the lumbar spine, femoral neck, and forearm were evaluated. RESULTS: AS males and females had lower BAP levels than their respective HC (p < 0.001 and p = 0.001). AS patients with bridging syndesmophytes had higher OC levels than AS patients either with non-bridging syndesmophytes (p = 0.001) or without spinal syndesmophytes (p < 0.001). OC and CTX levels correlated significantly with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). In the multivariate linear regression adjusted by age, gender, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BMD in the lumbar spine, and C-reactive protein (CRP), we observed an association between BAP levels and anti-tumour necrosis factor (anti-TNF) use (p = 0.05) whereas OC levels were associated with mSASSS (p < 0.001) and anti-TNF use (p = 0.05), and CTX levels were exclusively associated with mSASSS (p = 0.03). In the logistic regression analysis, only OC levels were associated with the presence of syndesmophytes in AS [odds ratio (OR) 2.42, 95% confidence interval (CI) 1.19-5.75]. CONCLUSIONS: We observed an increase in OC levels in AS patients with syndesmophytes. BTM levels were associated with the severity of spinal damage. Future longitudinal studies should evaluate whether these BTMs should be included as tools to determine the prognosis and progression of spinal damage.