The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population.

OBJECTIVE: Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population. METHODS: The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed. RESULTS: Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01-1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08-3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65-1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00-1.96, p = 0.0518). CONCLUSION: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.

Can we predict top-level sports performance in power vs endurance events? A genetic approach.

The goal of our study was to discriminate potential genetic differences between humans who are in both endpoints of the sports performance continuum (i.e. world-class endurance vs power athletes). We used DNA-microarray technology that included 36 genetic variants (within 20 different genes) to compare the genetic profile obtained in two cohorts of world-class endurance (N=100) and power male athletes (N=53) of the same ethnic origin. Stepwise multivariate logistic regression showed that the rs1800795 (IL6-174 G/C), rs1208 (NAT2 K268R) and rs2070744 (NOS3-786 T/C) polymorphisms significantly predicted sport performance (model χ(2) =25.3, df=3, P-value <0.001). Receiver-operating characteristic (ROC) curve analysis showed a significant discriminating accuracy of the model, with an area under the ROC curve of 0.72 (95% confidence interval: 0.66-0.81). The contribution of the studied genetic factors to sports performance was 21.4%. In summary, although an individual's potential for excelling in endurance or power sports can be partly predicted based on specific genetic variants (many of which remain to be identified), the contribution of complex gene-gene interactions, environmental factors and epigenetic mechanisms are also important contributors to the "complex trait" of being an athletic champion. Such trait is likely not reducible to defined genetic polymorphisms.

A common variant in the ABCA1 gene is associated with a lower risk for premature coronary heart disease in familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common autosomal codominant hereditary disease caused by defects in the LDL receptor (LDLR) gene, and one of the most common characteristics of affected subjects is premature coronary heart disease (CHD). In heterozygous FH patients, the clinical expression of FH is highly variable in terms of the severity of hypercholesterolaemia and the age of onset and severity of CHD. Identification of mutations in the ATP binding cassette transporter 1 (ABCA1) gene in patients with Tangier disease, who exhibit reduced HDL cholesterol and apolipoprotein A1 concentrations and premature coronary atherosclerosis, has led us to hypothesise that ABCA1 could play a key role in the onset of premature CHD in FH. In order to know if the presence of the R219K variant in the ABCA1 gene could be a protective factor for premature CHD in FH, we have determined the presence of this genetic variant by amplification by PCR and restriction analysis in a group of 374 FH subjects, with and without premature CHD. The K allele of the R219K variant was significantly more frequent in FH subjects without premature CHD (0.32, 95% CI 0.27 to 0.37) than in FH subjects with premature CHD (0.25, 95% CI 0.21 to 0.29) (p<0.05), suggesting that the genetic variant R219K in ABCA1 could influence the development and progression of atherosclerosis in FH subjects. Moreover, the K allele of the R219K polymorphism seems to modify CHD risk without important modification of plasma HDL-C levels, and it appears to be more protective for smokers than non-smokers.

[Thrombocytopenic purpura of the young infant caused by perinatal infection by cytomegaloviruses]. / Púrpura trombocitopénica del lactante menor causada por la infección perinatal por citomegalovirus.

Two cases of idiopathic trombocytopenic purpura, in infants 37 and 42 days old, and one case of atypical congenital cytomegaloviral disease are presented, the latter proved at necropsy. Cytomegalic inclusion cells are found in urine in both cases of purpura with hepatosplenomegaly and mononucleosis syndrome. In one of the cases, cytomegalovirus cultures are positive in urine and blood. The hemorrhagic syndrome is mild and recuperation is achieved in less than thirty days, without relapse. The use of corticosteroids is not recommended. With these two new cases, thirteen similar clinical observation of thrombocytopenic purpura in infants, six of them in 1977, are completed. Thus, a new entity is added to the growing list of clinical manifestations caused by human CMV infection.

Versión española del Swallowing Quality of Life Questionnaire: fase inicial de adaptación transcultural / Spanish version of the Swallowing Quality of Life Questionnaire (SWAL-QoL): Initial phase of cross-cultural adaptation

Introducción. El objetivo de este trabajo es realizar una versión en español del Swallowing Quality of Life Questionnaire (SWAL-QoL), desde su versión original en inglés, como fase inicial del proceso de adaptación transcultural a la población española. Material y métodos. El SWAL-QoL es un cuestionario autoadministrado diseñado para evaluar la calidad de vida en los pacientes afectos de disfagia orofaríngea. Consta de 44 ítems divididos en 11 dominios diferentes. Para la adaptación del cuestionario al castellano se ha utilizado el proceso de traducción-retrotraducción, valoración de la equivalencia semántica y conceptual por un comité multidisciplinar y estudio piloto en 5 pacientes afectos de disfagia orofaríngea. Resultados. Veintiocho ítems (63%) se consideraron literales, 15 ítems (34%) se describieron como semejantes y un ítem (2%) se consideró diferente. Tras realizar el estudio piloto no fue necesario modificar ningún ítem del cuestionario. La comprensión de los ítems adaptados al español fue correcta y los pacientes emplearon un tiempo medio de 21 ± 5 min en completar el cuestionario. Conclusiones. Hemos obtenido una versión en castellano del SWAL-QoL conceptualmente equivalente a la versión original, de uso relativamente sencillo y buena aceptación en la práctica clínica diaria, completando la primera fase de adaptación transcultural a la población española, quedando pendiente su validación para comprobar su validez y fiabilidad(AU)

Introduction. This project has aimed to obtain a Spanish version of the Swallowing Quality of Life Questionnaire (SWAL-QoL). We used the original English version as a starting point in order to begin with the first phase of a cross-cultural adaptation process to be used among Spanish patients. Material and methods. The SWAL-QoL is a self-administered questionnaire designed to evaluate the quality of life among the patients affected by oropharyngeal dysphagia. It is made up of 44 items divided into 11 specific domains. The adaptation of the questionnaire was performed by using a translation and back-translation process, assessment of semantic and conceptual equivalence by a multi-disciplinary committee and a pilot study evaluating 5 patients affected by oropharyngeal dysphagia. Results. Of the items considered, 28 (63%) were considered as having a literal translation, 15 (34%) as being similarly translated and 1 (2%) was considered to be different due to its translation. It was not necessary to change or modify any item of the questionnaire after the pilot study. The comprehension of the items translated into Spanish was correct and the patients took an average time of 21±5 minutes to complete the questionnaire. Conclusions. We have obtained a Spanish version of the SWAL-QoL questionnaire conceptually equivalent to the original English version. Its use is relatively simple with good acceptance in the daily clinical practice. The first step of its cross-cultural adaptation to Spanish patients has been completed, pending its validation in order to prove its validity and reliability(AU)