RESUMO
BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.
Assuntos
Artrite Reumatoide/sangue , Remodelação Óssea/fisiologia , Osteoporose/sangue , Fraturas por Osteoporose/diagnóstico , Osteoprotegerina/sangue , Ligante RANK/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Biomarcadores/sangue , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/patologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Pós-Menopausa/sangue , PrognósticoRESUMO
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. RESULTS: Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p = 0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p = 0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p = 0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p = 0.65). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p = 0.03). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 (p = 0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. CONCLUSION: Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.
Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Alelos , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Predisposição Genética para Doença , Esclerose Múltipla/etiologia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/metabolismo , Razão de Chances , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.
Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Adolescente , Adulto , Alelos , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Doença Crônica/tratamento farmacológico , Doença Crônica/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Dislipidemias/epidemiologia , Dislipidemias/genética , Feminino , Frequência do Gene , Hematócrito , Hemoglobinas/análise , Heterozigoto , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Fragmento de Restrição , Prednisona/uso terapêutico , Adulto JovemRESUMO
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.
RESUMO
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.
Assuntos
Artrite Reumatoide/genética , Densidade Óssea/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Fatores Etários , Idoso , Alelos , Artrite Reumatoide/complicações , Artrite Reumatoide/etnologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , México , Pessoa de Meia-Idade , Osteoporose/genéticaRESUMO
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.
Assuntos
Artrite Reumatoide/genética , Traumatismos da Mão/genética , Mãos/efeitos da radiação , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/etnologia , Feminino , Predisposição Genética para Doença , Traumatismos da Mão/etnologia , Traumatismos da Mão/etiologia , Humanos , Masculino , México/etnologia , Pessoa de Meia-IdadeRESUMO
Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p < 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07-1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05-2.3; p = 0.003), or CC (RR = 1.83; 95% CI = 1.07-3.14; p = 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03-1.72; p = 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.
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Artrite Reumatoide/tratamento farmacológico , Interleucina-6/genética , Isoxazóis/administração & dosagem , Metotrexato/administração & dosagem , Idoso , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Biomarcadores Farmacológicos/sangue , Feminino , Marcadores Genéticos , Genótipo , Humanos , Interleucina-6/sangue , Isoxazóis/efeitos adversos , Leflunomida , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
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.
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Densidade Óssea , Remodelação Óssea , Vértebras Cervicais/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Espondilite Anquilosante/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: There is a lack of information about the genotype frequencies of IL-6 -174G/C and -572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 -174G/C and -572G/C polymorphisms in Mexican mestizo with RA. METHODS: We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 -174G/C and -572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. RESULTS: The genotype -174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype -572GG (54% in patients versus 60.8% in controls, P = 0.295). CONCLUSIONS: This is the first study to evaluate the association of -174G/C and -572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.