RESUMO
BACKGROUND: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. AIM: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. PATIENTS & METHODS: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. RESULTS: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). CONCLUSION: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy.
Assuntos
Artrite Reumatoide/genética , Hidroximetil e Formil Transferases/genética , Metotrexato/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Complexos Multienzimáticos/genética , Nucleotídeo Desaminases/genética , Tetra-Hidrofolato Desidrogenase/genética , Adulto , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Biomarcadores Farmacológicos , Ciclina D1/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do TratamentoRESUMO
OBJECTIVE: The prevalence of secondary processes in women with postmenopausal osteoporosis (OP) is not well known. The aim of this study was to analyze the prevalence of conditions contributing to bone loss in postmenopausal women with OP and to evaluate the clinical characteristics and the impact of these disorders on the severity of the disease. METHODS: A total of 204 postmenopausal women (mean +/- SD age, 64.9 +/- 10 y) with OP were prospectively included. None had an evident secondary cause of OP. Bone mineral density assessment, spine x-ray, and laboratory tests including parathormone (PTH), 25-hydroxyvitamin D (25OHD), thyroid hormones, urinary N-terminal cross-linked telopeptide of type I collagen (NTx), and 24-hour urinary calcium and cortisol were performed in all participants before treatment. RESULTS: As a group, 82% had low 25OHD levels (<30 ng/mL), 35% had increased PTH levels (>65 pg/mL), and 20% had hypercalciuria (>250 mg/24 h). In addition, 41% had increased NTx urinary levels (>65 nmol/mmol). PTH levels were related to age and were higher in women with femoral Z score less than -2.0 (80.3 pg/mL vs 57.7 pg/mL; P = 0.03). Participants with increased urinary NTx showed lower lumbar T and Z scores, whereas women with low 25OHD levels had lower femoral neck bone mineral density and T score values. In addition, participants with vertebral fractures had higher prevalence of 25OHD levels less than 20 ng/mL (69.2% vs 53.4%; P < 0.05). CONCLUSIONS: Secondary processes that contribute to low bone mass in postmenopausal women with OP are frequent, especially vitamin D insufficiency, increased PTH values, and hypercalciuria. In addition, increased bone resorption is frequently observed in this group of women. Most of these processes contributed to the severity of the disease.