Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Ann Rheum Dis ; 80(9): 1168-1174, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34161253

RESUMEN

OBJECTIVE: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. METHODS: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. RESULTS: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. CONCLUSIONS: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.


Asunto(s)
Dolor de Espalda/diagnóstico , Dolor Crónico/diagnóstico , Herencia Multifactorial , Articulación Sacroiliaca/diagnóstico por imagen , Espondilitis Anquilosante/diagnóstico , Adulto , Pueblo Asiatico , Dolor de Espalda/genética , Dolor de Espalda/metabolismo , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Dolor Crónico/genética , Dolor Crónico/metabolismo , Femenino , Antígeno HLA-B27/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Reproducibilidad de los Resultados , Factores de Riesgo , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/metabolismo , Población Blanca
2.
Rheumatology (Oxford) ; 55(8): 1421-30, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27094595

RESUMEN

OBJECTIVE: Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. METHODS: We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Maori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). RESULTS: In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). CONCLUSION: Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.


Asunto(s)
Apolipoproteína A-I/genética , Gota/genética , Familia de Multigenes/genética , Adulto , Apolipoproteína C-III/genética , Apolipoproteínas C/genética , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Nativos de Hawái y Otras Islas del Pacífico/genética , Factores de Riesgo , Ácido Úrico/metabolismo , Población Blanca/genética
3.
Rheumatology (Oxford) ; 52(6): 1018-21, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23204548

RESUMEN

OBJECTIVE: To investigate the effect of hyperuricaemia on serum chemokine (C-C motif) ligand 2 (CCL2) levels and blood monocytes in people with gout. METHODS: Whole blood was collected from subjects with a history of acute or chronic gout but not currently experiencing an attack of gout, subjects with asymptomatic hyperuricaemia and healthy individuals with normouricaemia. Serum concentrations of CCL2 were measured by bead array and levels of CD14(+)/CD11b(+) blood monocytes determined by flow cytometry. RESULTS: Subjects with gout and asymptomatic hyperuricaemia had higher serum levels of CCL2 and showed an increase in the percentage of circulating CD14(+) monocytes compared with subjects with normouricaemia. CONCLUSION: Hyperuricaemia causes elevated serum CCL2 levels and increased monocyte recruitment that may be driven by soluble uric acid-induced CCL2 production. Hyperuricaemia may initiate subclinical priming of circulating blood monocytes for adhesion and trafficking during a gout attack.


Asunto(s)
Quimiocina CCL2/sangre , Gota/metabolismo , Hiperuricemia/metabolismo , Monocitos/metabolismo , Ácido Úrico/sangre , Anciano , Movimiento Celular , Femenino , Gota/sangre , Humanos , Hiperuricemia/sangre , Receptores de Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad
4.
Hum Mol Genet ; 19(24): 4813-9, 2010 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-20858603

RESUMEN

Genetic variation in ABCG2 (rs2231142, Q141K), encoding a uric acid transporter, is associated with gout in diverse populations. The aim of this study was to examine a role for ABCG2 in gout susceptibility in New Zealand Maori, Pacific Island and Caucasian samples. Patients (n = 185, 173 and 214, for Maori, Pacific Island and Caucasian, respectively) satisfied the American College of Rheumatology gout classification criteria. The comparison samples comprised 284, 129 and 562 individuals, respectively, without gout. rs2231142 was genotyped and stratification accounted for using genomic control markers. Association of the minor allele of rs2231142 with gout was observed in the Pacific Island samples (OR = 2.80, P(STRAT) < 0.001 after accounting for effects of population structure), but not in the Maori samples (OR = 1.08, P(STRAT)= 0.70), with heterogeneity in association evident between the Maori and Pacific Island datasets (P(HET) = 0.001). A similar dichotomy in association was observed when samples were stratified into Western (Tonga, Samoa, Niue, Tokelau) versus Eastern Polynesian (Maori, Cook Island) origin (OR = 2.59, P(STRAT) < 0.001; OR = 1.12, P(STRAT)= 0.48, respectively; P(HET) = 0.005). Association with gout was observed in the Caucasian samples (OR = 2.20, P = 3.2 × 10(-8)). Unlike SLC2A9, which is a strong risk factor for gout in both Maori and Pacific Island people, ABCG2 rs2231142 has a strong effect only in people of Western Polynesian ancestry. Our results emphasize the need to account for sub-population differences when undertaking biomedical genetic research in a group defined by a geographical region and shared ancestry but characterized by migratory events that create bottlenecks and altered genetic structure in the founder populations.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Etnicidad/genética , Predisposición Genética a la Enfermedad , Gota/etnología , Gota/genética , Proteínas de Neoplasias/genética , Población Blanca/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Preescolar , Emigración e Inmigración , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Filogenia , Polimorfismo de Nucleótido Simple/genética , Polinesia , Adulto Joven
5.
Ann Rheum Dis ; 69(9): 1711-6, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20472591

RESUMEN

OBJECTIVE: There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fcgamma receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of polymorphonuclear neutrophils (PMNs). Given recent evidence that low FCGR3B CN is a risk factor for systemic but not organ-specific autoimmune disease and the potential importance of PMN in the pathophysiology of rheumatoid arthritis (RA), the authors hypothesised that FCGR3B gene dosage influences susceptibility to RA. METHODS: FCGR3B CN was measured in 643 cases of RA and 461 controls from New Zealand (NZ), with follow-up analysis in 768 cases and 702 controls from the Netherlands and 250 cases and 211 controls from the UK. All subjects were of Caucasian ancestry. RESULTS: Significant evidence for an association between CN <2 and RA was observed in the Dutch cohort (OR 2.01 (95% CI 1.37 to 2.94), p=3 x 10-4) but not in the two smaller cohorts (OR 1.45 (95% CI 0.92 to 2.26), p=0.11 and OR 1.33 (95% CI 0.58 to 3.02), p=0.50 for the NZ and UK populations, respectively). The association was evident in a meta-analysis which included a previously published Caucasian sample set (OR 1.67 (95% CI 1.28 to 2.17), p=1.2 x 10-4). CONCLUSIONS: One possible mechanism to explain the association between reduced FCGR3B CN and RA is the reduced clearance of immune complex during inflammation. However, it is not known whether the association between RA and FCGR3B CN is aetiological or acts as a proxy marker for another biologically relevant variant. More detailed examination of genetic variation within the FCGR gene cluster is required.


Asunto(s)
Artritis Reumatoide/genética , Receptores de IgG/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Proteínas Ligadas a GPI , Dosificación de Gen , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
6.
ACR Open Rheumatol ; 2(12): 705-709, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33200883

RESUMEN

OBJECTIVE: To determine whether training increases accuracy of self-reported joint counts in people with rheumatoid arthritis (RA) and describe the knowledge and techniques for self-examination of joints for reporting of RA disease activity. METHODS: This mixed-methods study included 10 patients with RA and four rheumatologists. A rheumatologist presented about joint inflammation and disease monitoring in RA. Patients then self-examined and reported 28-tender joint count (28-TJC) and 28-swollen joint count (28-SJC). Next, two paired rheumatologists examined patients and reported 28-TJC and 28-SJC. After watching a joint examination video for training physicians, patients discussed their training needs for self-examination, with discussion analyzed using thematic analysis. Self-examination techniques were determined by consensus. Finally, patients self-examined and reported 28-TJC and 28-SJC. Reliability between the first and second patient-reported 28-TJCs and 28-SJCs and rheumatologist pair-reported 28-TJC and 28-SJC was determined with the intraclass coefficient. RESULTS: The reliability for patient self-reported joint counts was higher for the 28-TJC than for the 28-SJC. Reliability improved following rheumatologist examination and training. Patients identified a preference for practical information rather than detailed information on joint anatomy and pathophysiology. Clear definitions of "swollen" and "tender" were important; patients found the concept of "tenderness" difficult. Techniques for self-examination and reporting of joint counts were agreed on and demonstrated in an instructional video. CONCLUSION: Training increased reliability of patient-reported joint counts. Patients with RA identified important aspects of training for self-examination and reporting of joint counts. An 8-minute instructional video was codeveloped; the next step is the evaluation of the video's impact on patient-reported joint counts.

7.
N Z Med J ; 132(1507): 70-76, 2019 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-31830019

RESUMEN

AIM: To characterise the demographics, size and distribution of the New Zealand rheumatology workforce. METHOD: An online survey was sent to New Zealand rheumatologists in February 2018. RESULTS: The survey was completed by 63 of 64 practising New Zealand rheumatologists (response rate 98%). In public practice, the number of half-day clinics per FTE was five (R2 linear 0.87), so a half-day session in private practice was counted as 0.2 FTE. There were 28.71 FTE in the public sector, 14.97 in private and 43.68 total FTE. By district health board (DHB), public FTE per capita ranged from 0.20 FTE per 100,000 population in Nelson-Marlborough DHB to 0.96 in Whanganui DHB. None of the 20 DHBs met the Royal College of Physicians guideline of 1.16 FTE per 100,000 population in the public sector, and only four DHBs reached this level when private FTE were included. Rheumatologists under the age of 50 years were predominantly female (62% female), and older rheumatologists predominantly male (7.7% female, p<0.001). In the next five years 6.58 FTE public rheumatologists intended to retire, (94% male). 23/53 (43%) of public hospital rheumatologists offer appointments for non-inflammatory conditions, compared to 30/31 (97%) of private practice rheumatologists. Between 1999 and 2011, the FTE per 100,000 population increased by 35.4%, but the rate of improvement slowed in the interval between 2011 and 2018, increasing by 3.0%. CONCLUSION: The New Zealand rheumatologist workforce is becoming more gender-balanced but is below recommended FTE levels, is unevenly distributed, and previously documented improvements in overall FTE have now reached a plateau.


Asunto(s)
Necesidades y Demandas de Servicios de Salud , Fuerza Laboral en Salud/tendencias , Reumatólogos/provisión & distribución , Reumatología , Adulto , Distribución por Edad , Anciano , Femenino , Hospitales Públicos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Sector Público/estadística & datos numéricos , Distribución por Sexo , Encuestas y Cuestionarios
8.
PeerJ ; 6: e5088, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29967744

RESUMEN

BACKGROUND: Genome-wide association studies have identified a plethora of risk genes for both Crohn's disease (CD) and ankylosing spondylitis (AS). A subset of genes found to be risk factors for CD have also been found to be risk factors for AS. The objective of our study was to assess whether CD risk genes were associated with non-invasive clinical markers of gut inflammation in patients with AS, indicating a potential subset of patients with clinical as well as genetic overlap. METHODS: A total of 308 Caucasian patients who fulfilled the modified New York Criteria for AS, were assessed for bowel symptoms using the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ). Of these patients, 157 also had faecal calprotectin measured. All AS patients and 568 healthy controls were genotyped for 10 CD risk loci using predesigned single nucleotide polymorphism (SNP) genotyping assays. Chi-square analysis was used to test for association between genotype and DISQ score and faecal calprotectin level. RESULTS: The minor allele of two SNPs, one in chromosome region 1q32 SNP (rs11584383), and one in the gene coding for IL23R (rs11209026) conferred protection against AS. Only the association of 1q32 remained significant after Bonferroni correction for multiple testing. Stratification by DISQ score and faecal calprotectin did not influence the association of 1q32 with AS. CONCLUSION: In patients with AS, the association of the CD 1q32 SNP was independent of non-invasive markers of bowel inflammation. Other CD related SNPs were not found have a significant association with AS.

11.
Int J Rheum Dis ; 19(2): 205-10, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25873399

RESUMEN

AIM: To review inpatient management of acute gout in a New Zealand hospital. METHODS: A retrospective file review of all acute episodes of gout at Hutt Hospital, Wellington, New Zealand over a 1 year period. RESULTS: In the course of a year, there were 90 admissions for, or complicated by, acute gout. In 31 cases, gout was the primary diagnosis. Median length of stay was 5 days and readmissions were common. The majority of patients (87%) were known to have gout before admission, yet only 50% of these patients were on uric acid lowering treatment. Serum urate was measured in only 60% of patients with a mean level of 0.471 mmol/L. Treatment for the acute attack was evenly split between monotherapy (49%) and polytherapy (49%). Treatment modalities used were: prednisone (61%), non-steroidal anti-inflammatories (40%), colchicine (40%), adrenocorticotrophic hormone (ACTH) (15%) and intrarticular steroids (7%). Patients were generally treated in a timely manner with few patients experiencing delays. Patients seen by the Rheumatology Department were more likely to receive polytherapy, be treated with intra-articular steroids or ACTH and to start allopurinol. The 'treat-to-target' approach to the management of elevated serum urate was mentioned in only 9% of cases. CONCLUSION: There was considerable variability in the investigation and management of acute gout, with significant deviation from published protocols. The 'treat-to-target' approach to the management of elevated urate has not yet been widely adopted by the physicians in this New Zealand hospital.


Asunto(s)
Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Pacientes Internos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Quimioterapia Combinada , Revisión de la Utilización de Medicamentos , Femenino , Gota/sangre , Gota/diagnóstico , Adhesión a Directriz , Humanos , Tiempo de Internación , Masculino , Auditoría Médica , Persona de Mediana Edad , Nueva Zelanda , Readmisión del Paciente , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del Tratamiento , Regulación hacia Arriba , Ácido Úrico/sangre , Adulto Joven
12.
NPJ Genom Med ; 1: 16008, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-29263810

RESUMEN

Ankylosing spondylitis (AS) is a common chronic immune-mediated arthropathy affecting primarily the spine and pelvis. The condition is strongly associated with HLA-B*27 as well as other human leukocyte antigen variants and at least 47 individual non-MHC-associated variants. However, substantial additional heritability remains as yet unexplained. To identify further genetic variants associated with the disease, we undertook an association study of AS in 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. A novel association achieving genome-wide significance was noted at CDKAL1. Suggestive associations were demonstrated with common variants in FAM118A, C7orf72 and FAM114A1 and with a low-frequency variant in PNPLA1. Two of the variants have been previously associated with inflammatory bowel disease (IBD; CDKAL1 and C7orf72). These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having similar aetiopathogenesis.

13.
Eur J Hum Genet ; 11(11): 840-4, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14571268

RESUMEN

The product of the deleted in colorectal carcinoma (DCC) gene has a role in apoptosis and is a positional candidate for IDDM6, the putative chromosome 18q12-q23 autoimmune disease locus. We hypothesised that a nonconservative substitution (DCC 201 R --> G; nucleotide (nt) 601 C --> G), located in an extracellular immunoglobulin-like domain of DCC, is an aetiological determinant of autoimmunity. We tested this hypothesis by genetically testing the nt 601 C --> G polymorphism for association with three autoimmune phenotypes in a large population-based case-control study. There was no evidence for association of DCC nt 601 C --> G with autoimmune disease in cohorts comprising 2253 subjects with rheumatoid arthritis, type I diabetes and Graves' disease, and 2225 control subjects, from New Zealand and the United Kingdom. Furthermore, using the transmission disequilibrium test, there was no significant evidence for biased transmission of the nt 601 C --> G polymorphism to probands within a 382 family type I diabetes affected sibpair cohort from the United Kingdom. Thus, the DCC 201 R --> G polymorphism does not appreciably influence risk of developing the autoimmune diseases tested.


Asunto(s)
Enfermedades Autoinmunes/genética , Neoplasias Colorrectales/genética , Genes DCC , Polimorfismo Genético , Adulto , Edad de Inicio , Estudios de Casos y Controles , Niño , Preescolar , Genética de Población , Haplotipos , Heterocigoto , Humanos , Repeticiones de Microsatélite
15.
Clin Rheumatol ; 33(7): 963-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24609715

RESUMEN

The objective of this research is to measure the effect of a national ankylosing spondylitis (AS) public awareness campaign on numbers of referrals for suspected AS and numbers of cases diagnosed with axial spondyloarthritis (SpA). A television advertising campaign was conducted by Arthritis New Zealand in 2011 to raise public awareness of AS. A retrospective analysis was made of referrals received by the three rheumatology services 3 months before the campaign started and 3 months after the campaign ended. The age, gender, number of referrals for suspected AS and number of referrals resulting in a diagnosis of axial SpA were recorded. Independent analysis showed that the awareness campaign reached 82 % of the primary target audience. In the 3 months after the awareness campaign, there was a significant increase in referrals for suspected AS compared with the 3 months before the campaign (54 vs. 88, 63 %, p = 0.0056). Referrals for other conditions did not change. The number of referrals resulting in a diagnosis of axial SpA also increased (27 vs. 44, 63 %, p = 0.0576). The mean ages of the patients referred and of those diagnosed with axial SpA did not change. The male/female ratio was 1:1 among the referrals for suspected AS and 2:1 in referrals diagnosed with axial SpA, before and after the campaign. The Arthritis New Zealand AS public awareness campaign was associated with a significant increase in referrals to rheumatology services for suspected AS and an increase in the diagnosis of axial SpA in clinics.


Asunto(s)
Educación del Paciente como Asunto/métodos , Derivación y Consulta/estadística & datos numéricos , Reumatología/métodos , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Atención Primaria de Salud/métodos , Estudios Retrospectivos , Reumatología/organización & administración , Espondiloartritis/epidemiología , Espondilitis Anquilosante/epidemiología , Adulto Joven
16.
Joint Bone Spine ; 81(2): 160-3, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23932726

RESUMEN

OBJECTIVES: Gout is a major health problem in Polynesians and allopurinol, the drug of choice for the management gout, appears to be less effective in Polynesian patients. The uricosuric drug benzbromarone is an alternative treatment but CYP2C9 poor metabolisers (PMs) may be at a heightened risk of benzbromarone-induced hepatotoxicity. The objectives of this study were to determine the frequency of the PM alleles CYP2C9*2 and CYP2C9*3 in New Zealand (NZ) Caucasian and Polynesian gout cohorts; and then to test for novel CYP2C9 polymorphisms in Polynesians. METHODS: Eight hundred and fifty-two Caucasians (537 controls, 315 gout patients) and 1072 Maori and Pacific Island (Polynesian) people (620 controls, 452 gout patients) were genotyped for CYP2C9*2 and CYP2C9*3. Forty Polynesians were screened for novel CYP2C9 polymorphisms using whole genome sequencing. RESULTS: Frequency of CYP2C9 PM alleles was significantly higher in Caucasians compared to Polynesians (CYP2C9*2: 13.5% versus 3.1%; CYP2C9*3: 5.5% versus 1.6%, P<1.2E-11). Within Polynesians, CYP2C9 PM alleles were rarer in Western Polynesians (Samoa, Tonga) than Eastern Polynesians (NZ and Cook Island Maori; CYP2C9*2: 0.6% versus 2.5%; CYP2C9*3: 0.4% versus 2.0%; P<0.03). A total of 152 SNPs were found by sequencing. None of these variants were predicted by in silico analysis to significantly impact on CYP2C9 expression or activity. CONCLUSION: Prospective CYP2C9 genotyping of Caucasian gout patients may be warranted for benzbromarone, whereas the low frequencies of CYP2C9 PM alleles in Polynesians suggests that the CYP2C9 polymorphism may be of little or no relevance to benzbromarone prescribing in this population.


Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Benzbromarona/uso terapéutico , Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Gota/genética , Citocromo P-450 CYP2C9 , Humanos , Nueva Zelanda/etnología , Polimorfismo de Nucleótido Simple , Polinesia/etnología , Población Blanca
17.
Arthritis Res Ther ; 14(2): R92, 2012 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-22541845

RESUMEN

INTRODUCTION: Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets. METHODS: Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian. RESULTS: At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype. CONCLUSION: We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.


Asunto(s)
Sitios Genéticos/genética , Estudio de Asociación del Genoma Completo , Gota/etnología , Gota/genética , Transportadores de Anión Orgánico/genética , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo I/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Variación Genética/genética , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
18.
J Rheumatol ; 38(9): 1940-6, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21677001

RESUMEN

OBJECTIVE: To investigate whether there is an association between Raynaud's phenomenon (RP) and exposure to organic solvents in laboratory workers. METHODS: Technicians, scientists, and laboratory assistants working in histology, cytology, and transfusion medicine were surveyed about their use of solvents, particularly xylene and toluene, and about symptoms of RP. There were 341 responses. OR for having worked with solvents were calculated with logistic regression adjusted for age and sex. RESULTS: Laboratory workers who had worked with solvents had higher rates of severe RP, particularly those who had worked with xylene or toluene and either acetone (OR 8.8, 95% CI 1.9-41.1), or chlorinated solvents (OR 8.9, 95% CI 1.9-41.6), xylene or toluene and acetone compared to those who had worked with xylene or toluene but not acetone (OR 4.5, 95% CI 1.2-16.2), and similarly for chlorinated solvents (OR 4.5, 95% CI 1.2-16.3). RP symptoms occurring in the absence of cold exposure were more frequent for those who had worked with any solvent (OR 3.6, 95% CI 1.2-10.5) and just xylene or toluene (OR 2.8, 95% CI 1.1-7.3). Associations were also seen between increasing exposure to xylene or toluene and severe RP (OR 1.7, 95% CI 1.1-2.7, per 10 years) and with symptoms occurring in the absence of cold exposure (OR 1.7, 95% CI 1.2-2.5, per 10 years). CONCLUSION: We found that exposure to solvents may be associated with the development of RP, supporting previous work indicating that solvent exposure may be an etiological factor in systemic sclerosis.


Asunto(s)
Personal de Laboratorio Clínico , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Enfermedad de Raynaud/inducido químicamente , Esclerodermia Sistémica/inducido químicamente , Solventes/envenenamiento , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/epidemiología , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/epidemiología , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/epidemiología
19.
Arthritis Res Ther ; 13(3): R85, 2011 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-21658257

RESUMEN

INTRODUCTION: The C allele of the nonsynonymous Arg265His (rs3733591) variant of SLC2A9 confers risk for gout in Han Chinese, Solomon Island and Japanese samples, with a stronger role in tophaceous gout. There is no evidence for an association with gout in Caucasian populations. In the present study, we tested rs3733591 for association with gout in New Zealand (NZ) Maori, Pacific Island and Caucasian samples. METHODS: Rs3733591 was genotyped across gout patients (n = 229, 232 and 327 NZ Maori, Pacific Island and Caucasian samples, respectively) and non-gout controls (n = 343, 174 and 638 Maori, Pacific Island and Caucasian samples, respectively). Further Caucasian sample sets consisting of 67 cases and 4,712 controls as well as 153 cases and 6,969 controls were obtained from the Framingham Heart Study and the Atherosclerosis Risk in Communities study, respectively. The Polynesian samples were analyzed according to Eastern and Western Polynesian ancestry. RESULTS: No evidence for risk conferred by the C allele of rs3733591 with gout was found in the sample sets of NZ Maori (odd ratio (OR) = 0.98, P = 0.86), Eastern Polynesians (OR = 0.99, P = 0.92), Western Polynesians (OR = 1.16, P = 0.36) or combined Caucasians (OR = 1.15, P = 0.13). The C allele was significantly overrepresented in Maori tophaceous cases compared to cases without tophi (OR = 2.21, P = 0.008), but not in the other ancestral groupings. CONCLUSIONS: Noting that our study's power was limited for detecting weak genetic effects, we were unable to replicate associations of rs3733591 with gout in Eastern Polynesian, Western Polynesian and Caucasian samples. However, consistent with a previous study of Han Chinese and Solomon Island populations, our data suggest that rs3733591 could be a marker of severe gout in some populations. Our results also suggest that the effect of this variant is population-specific, further confirming population heterogeneity regarding the association of SLC2A9 with gout.


Asunto(s)
Proteínas Facilitadoras del Transporte de la Glucosa/genética , Gota/etnología , Gota/genética , Nativos de Hawái y Otras Islas del Pacífico/genética , Índice de Severidad de la Enfermedad , Población Blanca/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Nueva Zelanda/epidemiología , Mutación Puntual , Factores de Riesgo , Población Blanca/estadística & datos numéricos , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA