Association between RS3763040 polymorphism of the AQP4 and idiopathic intracranial hypertension in a Spanish Caucasian population.

Background: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown aetiology. Principal symptoms are headache, visual disturbances, and obesity, together with elevated intracranial pressure. Unspecified MRI, despite normal ventricle size, suggests alterations in the water flux cellular mediated by the brain water channel aquaporin-4 (AQP4). The association among IIH, cerebral spinal fluid malfunction, reabsorption, and functional or regulatory modifications of AQP4 is a hypothesis not confirmed. Methods: Blood samples were collected from 72 Spanish Caucasian patients with IIH. A genetic association study was performed with bi-allelic SNPs rs1049305 and rs10244884 in AQ1 and rs2075575, rs3763043, and rs3763040 in AQ4. Genetic data were compared with 94 healthy Caucasian control. Statistics studies were assessed by Pearson's χ 2 tests for 2 × 2 (alleles) or 3 × 2 (genotypes) contingency tables. A P value < 0.05 was considered to be statistically significant. Results: Statistically significant differences were found when comparing the results of the rs3763040 polymorphism of the AQ4 locus of IIH patients with controls, in genotypic frequencies (P = 0.0442) and allele frequencies (P = 0.0171). Furthermore, a statistically significant difference (P = 0.0207) was found in individuals carrying and not carrying the minor allele (GG + GA individuals vs GG homozygotes). No statistically significant differences were found when comparing allele and genotypic frequencies for SNPs rs1049305 and rs10244884 of AQ1 and rs2075575 and rs3763043 of AQ4. Conclusions: The association of AQP4 and specifically of its polymorphic variant rs3763040 with IIH should be validated in other ethnic groups in order to assess more precisely the role of AQP4 in the etiopathogenesis of IIH.

Criterios de derivación a genética clínica desde Atención Primaria. Documento de consenso / Referral criteria to clinical genetics from primary care: Consensus document

Introducción: La Atención Primaria (AP) es el primer contacto entre el paciente y el médico, por lo que es fundamental tener claro los criterios de sospecha de una enfermedad genética y dónde se debe remitir para su estudio. Material y métodos: Cuatro sociedades científicas: la Sociedad Española de Medicina Familiar y Comunitaria (semFYC), la Asociación Española de Genética Humana (AEGH), la Asociación Española de Pediatría (AEP) y la Sociedad Española de Oncología Médica (SEOM), han revisado los criterios de derivación a los servicios de genética clínica de las diferentes guías publicadas, con el objetivo de elaborar unas recomendaciones para AP. Conclusiones: Con este Documento de Consenso el médico de familia y el pediatra de AP conocerán cuándo, cómo y dónde derivar a sus pacientes con patología hereditaria y/o genética a los servicios de genética clínica.(AU)

Introduction: Primary care (PC) is the first contact between the patient and the doctor, so it is essential to be clear about the criteria for suspecting a genetic disease and where it should be referred for study. Material and methods: Four scientific societies: the Spanish Society of Family and Community Medicine (semFYC), the Spanish Association of Human Genetics (AEGH), the Spanish Association of Pediatrics (AEP) and the Spanish Society of Medical Oncology (SEOM), have reviewed the criteria for referral to the clinical genetics services of the different published guidelines with the purpose of define the recommendations for PC. Conclusions: With this consensus document, the PC doctor and pediatrician will know when, how and where to refer their patients with hereditary and/or genetic pathology to clinical genetics services.(AU)

[Referral criteria to clinical genetics from primary care: Consensus document]. / Criterios de derivación a genética clínica desde Atención Primaria. Documento de consenso.

INTRODUCTION: Primary care (PC) is the first contact between the patient and the doctor, so it is essential to be clear about the criteria for suspecting a genetic disease and where it should be referred for study. MATERIAL AND METHODS: Four scientific societies: the Spanish Society of Family and Community Medicine (semFYC), the Spanish Association of Human Genetics (AEGH), the Spanish Association of Pediatrics (AEP) and the Spanish Society of Medical Oncology (SEOM), have reviewed the criteria for referral to the clinical genetics services of the different published guidelines with the purpose of define the recommendations for PC. CONCLUSIONS: With this consensus document, the PC doctor and pediatrician will know when, how and where to refer their patients with hereditary and/or genetic pathology to clinical genetics services.

Genetic profiles to identify talents in elite endurance athletes and professional football players.

The genetic profile that is needed to identify talents has been studied extensively in recent years. The main objective of this investigation was to approach, for the first time, the study of genetic variants in several polygenic profiles and their role in elite endurance and professional football performance by comparing the allelic and genotypic frequencies to the non-athlete population. In this study, genotypic and allelic frequencies were determined in 452 subjects: 292 professional athletes (160 elite endurance athletes and 132 professional football players) and 160 non-athlete subjects. Genotyping of polymorphisms in liver metabolisers (CYP2D6, GSTM1, GSTP and GSTT), iron metabolism and energy efficiency (HFE, AMPD1 and PGC1a), cardiorespiratory fitness (ACE, NOS3, ADRA2A, ADRB2 and BDKRB2) and muscle injuries (ACE, ACTN3, AMPD1, CKM and MLCK) was performed by Polymerase Chain Reaction-Single Nucleotide Primer Extension (PCR-SNPE). The combination of the polymorphisms for the "optimal" polygenic profile was quantified using the genotype score (GS) and total genotype score (TGS). Statistical differences were found in the genetic distributions between professional athletes and the non-athlete population in liver metabolism, iron metabolism and energy efficiency, and muscle injuries (p<0.001). The binary logistic regression model showed a favourable OR (odds ratio) of being a professional athlete against a non-athlete in liver metabolism (OR: 1.96; 95% CI: 1.28-3.01; p = 0.002), iron metabolism and energy efficiency (OR: 2.21; 95% CI: 1.42-3.43; p < 0.001), and muscle injuries (OR: 2.70; 95% CI: 1.75-4.16; p < 0.001) in the polymorphisms studied. Genetic distribution in professional athletes as regards endurance (professional cyclists and elite runners) and professional football players shows genetic selection in these sports disciplines.

Genetic Profile in Genes Associated with Cardiorespiratory Fitness in Elite Spanish Male Endurance Athletes.

BACKGROUND: most of the research concerning the influence of genetics on endurance performance has been carried out by investigating target genes separately. However, endurance performance is a complex trait that can stem from the interaction of several genes. The objective of this study was to compare the frequencies of polymorphisms in target genes involving cardiorespiratory functioning in elite endurance athletes vs. non-athlete controls. METHODS: genotypic frequencies were determined in 123 elite endurance athletes and in 122 non-athletes. Genotyping of ACE (rs4340), NOS3 (rs2070744 and rs1799983), ADRA2a (rs1800544 and rs553668), ADRB2 (rs1042713 and rs1042714), and BDKRB2 (rs5810761) was performed by polymerase chain reaction. The total genotype score (TGS: from 0 to 100 arbitrary units; a.u.) was calculated from the genotype score in each polymorphism. RESULTS: the mean TGS in non-athletes (47.72 ± 11.29 a.u.) was similar to elite endurance athletes (46.54 ± 11.32 a.u., p = 0.415). The distribution of TGS frequencies were also similar in non-athletes and elite endurance athletes (p = 0.333). There was no TGS cut-off point to discriminate being elite endurance athletes. CONCLUSIONS: the genetic profile in the selected genes was similar in elite endurance athletes and in controls, suggesting that the combination of these genes does not determine endurance performance.

Genotype scores in energy and iron-metabolising genes are higher in elite endurance athletes than in nonathlete controls.

Information about the association of energy and iron-metabolising genes with endurance performance is scarce. The objective of this investigation was to compare the frequencies of polymorphic variations of genes involved in energy generation and iron metabolism in elite endurance athletes versus nonathlete controls. Genotype frequencies in 123 male elite endurance athletes (75 professional road cyclists and 48 elite endurance runners) and 122 male nonathlete participants were compared by assessing 4 genetic polymorphisms: AMPD1 c.34C/T (rs17602729), PPARGC1A c.1444G/A (rs8192678) HFEH63D c.187C/G (rs1799945) and HFEC282Y c.845G/A (rs1800562). A weighted genotype score (w-TGS; from 0 to 100 arbitrary units (a.u.)) was calculated by assigning a corresponding weight to each polymorphism. In the nonathlete population, the mean w-TGS value was lower (39.962 ± 14.654 a.u.) than in the group of elite endurance athletes (53.344 ± 17.053 a.u). The binary logistic regression analysis showed that participants with a w-TGS > 38.975 a.u had an odds ratio of 1.481 (95% confidence interval: 1.244-1.762; p < 0.001) for achieving elite athlete status. The genotypic distribution of polymorphic variations involved in energy generation and iron metabolism was different in elite endurance athletes vs. controls. Thus, an optimal genetic profile in these genes might contribute to physical endurance in athlete status. Novelty Genetic profile in energy generation and iron-metabolising genes in elite endurance athletes is different than that of nonathletes. There is an implication of an "optimal" genetic profile in the selected genes favouring endurance sporting performance.

Liver-Metabolizing Genes and Their Relationship to the Performance of Elite Spanish Male Endurance Athletes; a Prospective Transversal Study.

BACKGROUND: The genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population. METHODS: Genotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the "optimal" polygenic profile has been quantified using the genotype score (GS). RESULTS: Statistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213-4.760 (p = 0.002)) in the polymorphisms studied. CONCLUSIONS: Genotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity.

Relevancia de las nuevas pruebas genéticas en el diagnóstico de la talla baja con dismorfias / Relevance of new genetic tests in the diagnosis of short stature with dysmorphic features

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Cytokine gene polymorphisms in retinal detachment patients with and without proliferative vitreoretinopathy: a preliminary study.

PURPOSE: Cytokines and other growth factors such as interleukins play an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). Interindividual variations in cytokine production seem to correlate with some cytokine gene polymorphisms. The purpose of this study was to analyse the distribution of these cytokine gene variants in patients with rhegmatogenous retinal detachment (RD) with and without PVR. METHODS: Single nucleotide polymorphisms were analysed for five cytokines: tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), interferon-gamma (IFN-gamma), interleukin-6 (IL-6) and interleukin-10 (IL-10). Patients were divided into two surgically treated groups of RD patients: group RD had 27 patients with RD, and group PVR had 31 patients with RD complicated by PVR. A control group was composed of 46 ethnically matched healthy individuals. RESULTS: The genotype distribution of the TGF-beta1 codon 10 polymorphism differed between PVR and RD patients (p = 0.018) and between PVR patients and controls in codon 25 (p = 0.011). There was a higher frequency of TGF-beta1 codon 10 allele T in PVR patients compared with RD patients (p = 0.023). No statistically significant differences between groups were observed for the other polymorphisms examined. CONCLUSION: An association between the TGF-beta1 genetic profile and the development of PVR was detected in this study. Further studies are necessary to confirm this finding and to establish its clinical relevance.