Polymorphisms in autophagy genes are genetic susceptibility factors in glioblastoma development.

BACKGROUND: Glioblastoma is the most aggressive and common malignant primary brain tumor in adults. Many genetic, epigenetic and genomic mutations have been identified in this tumor, but no driving cause has been identified yet for glioblastoma pathogenesis. Autophagy has proved to be deregulated in different diseases such as cancer where it has a dual role, acting as a tumor suppression mechanism during the first steps of tumor development and promoting cancer cells survival in stablished tumors. METHODS: Here, we aimed to assess the potential association between several candidate polymorphisms in autophagy genes (ATG2B rs3759601, ATG16L1 rs2241880, ATG10 rs1864183, ATG5 rs2245214, NOD2 rs2066844 and rs2066845) and glioblastoma susceptibility. RESULTS: Our results showed a significant correlation between ATG2B rs3759601, ATG10 rs1864183 and NOD2 rs2066844 variants and higher risk to suffer glioblastoma. In addition, the relationship between the different clinical features listed in glioblastoma patients and candidate gene polymorphisms was also investigated, finding that ATG10 rs1864183 might be a promising prognosis factor for this tumor. CONCLUSIONS: This is the first report evaluating the role of different variants in autophagy genes in modulating glioblastoma risk and our results emphasize the importance of autophagy in glioblastoma development.

Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.

BACKGROUND: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor. PATIENTS AND METHODS: CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and four dosing schedules, two weekly (2 days on/5 days off; 3 days on/4 days off), one biweekly (3 days on/11 days off), and one monthly (4 days on/24 days off). The primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early antitumor activity, pharmacokinetics, and pharmacodynamics. RESULTS: This study enrolled 69 patients, 67 with solid tumors and two with diffuse large B-cell lymphoma (DLBCL). The median age was 57 years (range, 21-80) and the median number of prior regimens was four (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in more than two patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of 8 October 2019, one patient with grade 2 astrocytoma achieved a complete response, one patient with endometrial carcinoma had a partial response, and six patients had prolonged stable disease ≥11 months. CONCLUSIONS: CC-90010 is well tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.

Gastrointestinal nematode infection and feeding behaviour of goats in a heterogeneous vegetation: No evidence of therapeutic self-medication.

The aim of this study was to identify modifications in the feeding behaviour of goats browsing a tropical deciduous forest (TDF) when natural gastrointestinal nematode (GIN) infection was suppressed. Continuous bite monitoring through direct observation was implemented in 12 Criollo goats (adults, non-pregnant) foraging for 4 h per day during the rainy season. In the first Period (P1, one observation point) all goats were maintained with natural GIN infection. In the second Period (P2, three observation points), goats were equally distributed into 2 groups: i) moxidectin treated group (TG) used in a suppressive scheme; and ii) naturally infected group (IG). For each observation point, goats were monitored at three timepoints per day (80 min each), for three consecutive days, to estimate their intake of dry matter (DM), condensed tannins (CT), crude protein, metabolizable energy and digestible DM. Live weight (LW), faecal samples and blood samples were obtained every 28 days to determine LW change, faecal egg counts (FEC) and packed cell volume (PCV). During P1 and P2, the TG and IG had similar LW change and PCV. During both periods, the intake of DM, CT and all macronutrients were similar for TG and IG. The suppression of GIN infection did not modify the feeding behaviour of goats. Therefore, a therapeutic self-medicative behaviour was not identified in Criollo goats browsing a TDF.

Evidence of the high prevalence of neurological disorders in nonsyndromic X-linked recessive ichthyosis: a retrospective case series.

BACKGROUND: X-linked recessive ichthyosis (XLI) is a relatively common type of ichthyosis caused by a deficiency in the steroid sulfatase (STS) enzyme. It is the only type of ichthyosis that can be both syndromic and nonsyndromic. Typical clinical features include dark-brown scale of variable size favouring the extensor surfaces of the extremities. OBJECTIVES: To characterize clinically nonsyndromic XLI, with a particular focus on extracutaneous manifestations. METHODS: This was a multicentre retrospective review of clinical findings from a case series of patients with a clinical and genetic diagnosis of XLI. RESULTS: We identified 30 patients with XLI belonging to 25 different families carrying a deletion in the STS locus. All patients had dark scales of variable size on the extensor surfaces of the extremities. Lack of flexural involvement and pruritus were common but inconsistent findings, whereas palmoplantar hyperlinearity was absent in all but one patient. A history of orchiopexy was present in 10% and thus was more common than expected vs. the general population (3%). Neurological disorders including epilepsy (13%) and attention deficit hyperactivity disorder (ADHD; 30%) were over-represented in patients with XLI. CONCLUSIONS: This was a retrospective study with a limited number of patients. In the absence of confirmatory genetic testing and family history of the disease, dark-brown scale of the extensor surfaces and the absence of palmoplantar hyperlinearity appear to be the most reliable clinical findings supporting a diagnosis of XLI. Dermatologists should be aware of the high prevalence of ADHD and epilepsy in patients with nonsyndromic XLI.

Análisis de la relación entre polimorfismos en regiones diana de micro-ARN y la enfermedad hepática alcohólica / Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease

Introducción. El consumo de alcohol induce una respuesta inflamatoria mediada por los receptores de tipo Toll4 (TLR4) y el factor nuclear (NF)-?B, originando daño orgánico. Algunos micro-ARN (miARN) modulan la respuesta inflamatoria mediante retroalimentación negativa de mediadores como las interleucinas (IL). Así pues, polimorfismos en los genes de algunas IL localizados cerca de las dianas de los miARN podrían modificar el riesgo de daño orgánico inducido por el alcohol. Este estudio analizó la posible relación entre el alcoholismo o la enfermedad hepática alcohólica (EHA) y los polimorfismos IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328) y NFKB1 3400 A>G (rs4648143). Pacientes y métodos. Se incluyeron 301 pacientes alcohólicos varones y 156 voluntarios sanos varones. Los polimorfismos fueron genotipados mediante discriminación alélica utilizando el sistema de PCR TaqMan(R). Se compararon las frecuencias alélicas y genotípicas entre grupos y se realizó un análisis de regresión logística para dilucidar el modelo de herencia. Resultados. El análisis del polimorfismo de IL1R1 (rs3917328) mostró que la proporción de portadores del aleloT (genotipos CT y TT) era mayor en los controles sanos (9,7%) que en pacientes alcohólicos (6,5%, p=0,042). Sin embargo el análisis de regresión logística no mostró resultados significativos. No se encontraron diferencias significativas entre grupos con respecto al resto de polimorfismos estudiados. Conclusiones. Nuestro estudio describe, por primera vez, las frecuencias esperadas de polimorfismos en regiones diana de miARN en pacientes alcohólicos con y sin EHA. Serán necesarios nuevos estudios para aclarar la relevancia de estos polimorfismos en el desarrollo de alcoholismo o EHA

Introduction. Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. Patients and methods. The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan(R) PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. Results. Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. Conclusions. Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development

A protocol of human animal interaction to habituate young sheep and goats for behavioural studies.

Animal habituation is key to obtain reliable data on behavioural studies but detailed procedures to achieve it are scarce. This study designed a set of actions to habituate sheep and goats to human observers. Pelibuey sheep (n = 15) and Criollo goats (n = 10) were classified as (a) avoider, flight from human interaction, or (b) follower, seek human interaction. Habituation was measured by the reduction of flight distance by avoiders, or number of followers in the presence of observers. The habituation protocol consisted of a gradually increased series of five manoeuvres, either challenge (for avoiders) or evasion (for seekers), performed first inside a pen and subsequently in a grass paddock. Habituation was considered successful when animals could be observed from a 1-m distance without flight or following the observer. In the pen, habituation took 12 and 13 days for sheep and goats, respectively. Meanwhile, in the grass paddock habituation took 10 days, for both species. The number of challenge and evasion series was negatively correlated with the flight distance in sheep and with the number of followers in goats. This protocol is simple and practical to implement and enables animal habituation for behavioural studies.

Síndrome de Gorlin / Gorlin Syndrome

El síndrome de Gorlin es una enfermedad infrecuente de herencia autosómica dominante producida por mutaciones en genes de la vía de señalización Sonic Hedgehog, entre los que destaca PTCH1. Se caracteriza por el desarrollo de múltiples carcinomas basocelulares en edades tempranas, que pueden ir asociados a otras manifestaciones cutáneas como pits palmoplantares, o a manifestaciones extracutáneas, entre las que destacan los queratoquistes odontogénicos y el meduloblastoma. El papel del dermatólogo es importante en la sospecha de este síndrome, pero suele ser necesario un equipo multidisciplinar en el diagnóstico, seguimiento y en el tratamiento de estos pacientes. El tratamiento dermatológico puede ser complicado debido al alto número de carcinomas basocelulares y a su extensión. En los últimos años se han desarrollado nuevos fármacos que inhiben la vía Sonic Hedgehog y parecen prometedores para estos pacientes, aunque su eficacia está limitada por los efectos secundarios y la creación de resistencias

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The disease is characterized by the development of multiple basal cell carcinomas at young ages. These tumors may present with other skin manifestations such as palmoplantar pits and with extracutaneous manifestations such as odontogenic keratocysts and medulloblastoma. Although the dermatologist may be key for recognizing clinical suspicion of the syndrome, a multidisciplinary team is usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be complicated due to the large number of basal cell carcinomas and the extent of involvement. In recent years, new drugs that inhibit targets in the sonic hedgehog pathway have been developed. Although these agents appear promising options for patients with Gorlin syndrome, their efficacy is limited by adverse effects and the development of resistance

Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease. / Análisis de la relación entre polimorfismos en regiones diana de micro-ARN y la enfermedad hepática alcohólica.

INTRODUCTION: Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. PATIENTS AND METHODS: The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. RESULTS: Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. CONCLUSIONS: Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development.

Gorlin Syndrome. / Síndrome de Gorlin.

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The disease is characterized by the development of multiple basal cell carcinomas at young ages. These tumors may present with other skin manifestations such as palmoplantar pits and with extracutaneous manifestations such as odontogenic keratocysts and medulloblastoma. Although the dermatologist may be key for recognizing clinical suspicion of the syndrome, a multidisciplinary team is usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be complicated due to the large number of basal cell carcinomas and the extent of involvement. In recent years, new drugs that inhibit targets in the sonic hedgehog pathway have been developed. Although these agents appear promising options for patients with Gorlin syndrome, their efficacy is limited by adverse effects and the development of resistance.

Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome.

BACKGROUND: Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental alterations and multiple basal cell carcinomas. Mutations in PTCH1, which encodes a membrane receptor for Sonic Hedgehog, are associated with the development of the disease. Most of them produce a truncated protein, which is unable to suppress Smoothened protein and continuously activates the downstream pathway. OBJECTIVES: We aimed to characterize 22 unrelated Spanish patients with NBCCS, the largest cohort with Gorlin syndrome reported to date in Spain. METHODS: Genomic analysis of PTCH1 was performed in patients with NBCCS and controls, and mutations were analysed using bioinformatics tools. RESULTS: We report for the first time two young patients, one each with uterus didelphys and ganglioneuroma, within the context of NBCCS. One patient showing a severe phenotype of the disease had developed basal cell carcinomas since childhood. Sanger sequencing of PTCH1 in this cohort identified 17 novel truncating mutations (11 frameshift, five nonsense and one mutation affecting an exon-intron splice site) and two novel missense mutations that were predicted to be pathogenic. The patients showed great clinical variability and inconsistent genotype-phenotype correlation, as seen in relatives carrying similar mutations. CONCLUSIONS: This study contributes to increase the pool of clinical manifestations of NBCCS, as well as increasing the number of pathogenic mutations identified in PTCH1 predisposing to the condition. The inconsistencies found between phenotype and genotype suggest the involvement of other modifying factors, genetic, epigenetic or environmental.

Familial seborrhoeic keratosis associated with multiple 'pure reticulated acanthomas' and infundibulocystic basal cell carcinomas.

BACKGROUND: A variety of genodermatoses with multiple cutaneous tumours and germline genetic alterations, such as PTCH1 mutations, have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis. OBJECTIVES: To describe the clinical, dermoscopic and histopathological features of multiple cutaneous lesions, mostly infundibulocystic basal cell carcinomas (ICBCCs) and pure reticulated acanthomas, present in a family affected by familial seborrhoeic keratosis. In addition, we tested for possible germline alterations in FGFR3 and PTCH1. METHODS: Ten members of one family were clinically examined and 92 skin biopsy specimens were evaluated. Blood samples from six individuals were analysed for FGFR3 and PTCH1 germline alterations. We reviewed the literature concerning genetic FGFR3 alterations in seborrhoeic keratosis. RESULTS: Individuals of all generations affected by familial seborrhoeic keratosis also presented other skin tumours that corresponded histologically to reticulated acanthomas without apocrine or sebaceous differentiation, as well as ICBCCs. In addition, two novel germline variants, p.Pro449Ser (c.1345C>T) in FGFR3 and p.Pro725Ser (c.2173C>T) in exon 14 of PTCH1 were identified in five participants. CONCLUSIONS: We characterize for the first time the clinical, dermoscopic and histopathological features of multiple reticulated acanthomas without apocrine or sebaceous differentiation, for which we propose the term 'pure reticulated acanthoma', and ICBCCs associated with familial seborrhoeic keratosis. We identified FGFR3 and PTCH1 germline polymorphisms whose influence in the development of reticulated acanthomas is unknown.

Gastrointestinal nematode populations with multiple anthelmintic resistance in sheep farms from the hot humid tropics of Mexico.

This study evaluated the status of anthelmintic resistance against the three available classes of commercial drugs in seven sheep farms in the hot humid tropics of Mexico. Drug classes included benzimidazole (BZ), ivermectin (IVM) and levamisole (LV). Respective faecal egg count reduction tests (FECRT) were performed in each farm. Faecal samples were obtained from the rectum of >100 sheep in each farm. Adult sheep shedding >150 eggs per gram of faeces (EPG) were included. In each farm, animals were allotted to one of four groups with similar mean EPG: Control Group (untreated), BZ group (albendazole sulfoxide 5mg/kg LW), IVM group (ivermectin, 0.2mg/kg LW) and LEV group (levamisole 7.5mg/kg LW). Drugs were administered subcutaneously. A second faecal sampling was performed on the same animals of each farm 14days post-treatment. The GIN genera obtained from faecal cultures were identified for each group in different farms. Percentage faecal egg count reduction (%R) and 95% confidence intervals were estimated using the RESO© software. A questionnaire was applied to farm owners to describe anthelmintic management practices. All sheep farms had GIN populations with multiple resistance to the three anthelmintic classes tested. The %R ranged from 0 to 48% for BZ, 29 to 82% for IVM and 1 to 88% for LEV. Haemonchus spp. and Trichostongylus spp. were found in all treated groups of the study farms. Resistant Oesophagostomum spp. larvae (BZ or IVM) were found in respective farms. Treatment practices in study farms included frequent mass treatment every two months with extra treatments applied individually in the presence of clinical signs. Drug dosage used visual estimation of body weight rather than the exact weight of each animal. Quarantine anthelmintic treatment of incoming stock was used but efficacy was not confirmed.

Epidermal growth factor receptor (EGFR) pathway polymorphisms as predictive markers of cetuximab toxicity in locally advanced head and neck squamous cell carcinoma (HNSCC) in a Spanish population.

OBJECTIVES: To examine the relationship between polymorphisms of the epidermal growth factor receptor (EGFR) pathway and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with cetuximab. MATERIAL AND METHODS: Multicenter, retrospective, observational pilot study which included 110 patients with histologically-confirmed human papillomavirus (HPV) negative HNSCC in locally advanced stages (III-IVA-B) and who were treated with chemotherapy and radiotherapy plus cetuximab between 2003 and 2013. Genetic analyses for single nucleotide polymorphisms (SNP) in genes EGFR, CCDN1, FCGR2A, FCGR3A and KRAS-LCS6 were performed though available allelic discrimination assay and/or polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Acneiform rash was observed in 55.5% of patients, dry skin in 45.5% and pruritus in 20.9%. A significant association with dry skin and global cetuximab-related toxicity was observed for the KRAS-LCS6 (rs61764370) variant (p<0.05); carriers of the G allele (genotypes TG+GG) in the dominant model were observed to have a decreased susceptibility of developing dry skin (OR=0.287 [95%CI=0.119-0.695]). Carriers of the A (GA+AA) allele for EGFR (rs2227983) showed a decreased risk of suffering from pruritus (OR=0.345 [0.124-0.958]). Similarly, KRAS (rs1801274) was related with lower global cetuximab-related toxicity (OR=0.266 [0.114-0.622]). CONCLUSION: This pilot study provides preliminary evidence supporting genetic variation of EGFR (rs2227983), KRAS (rs61764370) and FCGR2A (rs180127) as useful biomarkers for predicting reduced skin toxicity in HNSCC patients treated with a cetuximab-based therapy. Alternative therapeutic options should be explored for these patients.

Association of IL1Β (-511 A/C) and IL6 (-174 G > C) polymorphisms with higher disease activity and clinical pattern of psoriatic arthritis.

The objective of this study is to analyze whether IL1ß (-511G > A) and IL6 (-174 G > C) polymorphisms are associated with inflammatory activity, radiographic damage or clinical pattern of psoriatic arthritis (PsA). One hundred twenty-five patients classified as PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included. Patients were stratified according to their clinical pattern at inclusion as peripheral, axial, or mixed involvement. Disease activity in peripheral or mixed forms was measured using the number of swollen and tender joints, pain analog visual scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score 28 (DAS28). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used for axial and mixed forms, as were pain visual analog scale, ESR and CRP. Radiographic damage was evaluated using a modified Sharp score and modified stoke ankylosing spondylitis spinal score (SASSSm). The polymorphisms for the promoter region of IL1ß (-511 G/A) and IL-6 (-174 G/C) were analyzed. The G allele of IL1B (-511G/A) polymorphism was associated with higher peripheral joint disease activity (OR 3.13; p < 0.0004; CI 95 % 1.43-6.82, p (corrected) <0.008), while the G allele of the IL6 (174G > C) polymorphism presented a strong trend to be associated with peripheral forms (70.86 %) (OR 1.89; p < 0.03; CI 95 % 1.06-3.39, p-corrected 0.05). In addition, this allele showed a lower association with HLA-B27 (15.78 %) compared with C allele (28.57 %) (OR 0.469; p = 0.02; CI 95 % 0.238-0.923, p-corrected 0.03). This study suggests that the G allele polymorphism of IL1B (-511 A/C) is associated with higher peripheral joint disease activity. On the other hand, the IL6 (-174 G/C) polymorphism showed a strong trend to be associated with the peripheral pattern of PsA.

Relación de la presencia de polimorfismos de CFH, HTRA1, ARMS2,VEGF-A y VEGF-R con la aparición de los subtipos de degeneración macular asociada a la edad / The presence of CFH, HTRA1, ARMS2, VEGF-A and VEGF-R and the appearance of age-related macular degeneration sub-types

OBJETIVO: Demostrar la influencia genética en el desarrollo de los distintos tipos de degeneración macular asociada a la edad (DMAE) analizando las distribuciones genotípicas de polimorfismos de CFH,ARMS2, HTRA1, VEGF-A y VEGF-R en pacientes con DMAE exudativa y DMAE atrófica. MÉTODO: Se toman 101 pacientes diagnosticados de DMAE (74 exudativa y 27 atrófica) según las normas del sistema internacional de clasificación Wisconsin. Analizamos los polimorfismos rs1410996 del genCFH, rs10940923 de ARMA2, rs833061 y rs699947 de VEGF-A y rs2071559 de VEGF-R mediante PCR a tiempo real con sondas Taqman y el HTRA1 rs112000638 mediante digestión con endonucleasas de restricción. Analizamos la distribución genotípica de los distintos polimorfismos en nuestro grupo de pacientes con DMAE exudativa y los que presentan DMAE atrófica y comparamos los resultados para cada uno de los genes a estudio. RESULTADOS: No encontramos diferencias estadísticamente significativas (p > 0,05) en la distribución genotípica de los distintos polimorfismos entre pacientes con DMAE atrófica y pacientes con DMAE exudativa en nuestra población, si bien los genotipos considerados «de riesgo» por otros estudios tienden a aparecer de forma más frecuente en la DMAE exudativa, a pesar de no obtener diferencias significativas. CONCLUSIONES: Las variantes alélicas de los genes CFH, ARMS2, HTRA1, VEGF-A o VEGF-R no se asocian con los diferentes subtipos de DMAE, lo que indica que, aunque parece que están implicados en la susceptibilidad a padecer la enfermedad, no están implicados en el desarrollo de las variantes clínicas en nuestra población. Son necesarios nuevos estudios en diferentes poblaciones y con un mayor tamaño muestral para confirmar estos resultados

OBJECTIVE: To demonstrate the genetic influence in the onset of the different age-related macular disease (AMD) subtypes by analysing the genotype distribution of CFH, ARMS2, HTRA1, VEGF-A and VEGF-Rpolymorphisms in patients with neovascular and atrophic AMD. MATERIALS AND METHODS: The study was conducted on 101 consecutive patients with AMD diagnosis (74 exudative, 27 atrophic) following Wisconsin international classification criteria. The CFH rs1410996, ARMS2 rs10940923,VEGF-A rs833061, rs699947, and VEGF-R rs2071559 polymorphisms were analysed using real time PCR with taqman probes, and HTRA1 rs112000638 using restriction endonucleases digestion. A study was made of the genotype distribution of the different polymorphisms in our group of patients with neovascular AMD and those with the atrophic type, and a comparison was made of the results for each one of the genes studied. RESULTS: No statistically significant differences (P>.05) were found in the genotype distribution of the different polymorphisms between patients with neovascular AMD and patients with atrophic AMD in our population, although the 'risk' genotypes tended to appear more frequently in patients with neovascular AMD, despite the lack of statistical significance. CONCLUSIONS: Allelic variants of CFH, ARMS2, HTRA1, VEGF-A or VEGF-R genes are not associated with the different AMD subtypes. This suggests that, although the polymorphisms seem to be associated with the disease susceptibility, they are not involved in the onset of the different clinical variants of AMD. Further studies in different populations, and with a larger cohort of patients, are needed to confirm these results

The presence of CFH, HTRA1, ARMS2, VEGF-A and VEGF-R and the appearance of age-related macular degeneration sub-types.

OBJECTIVE: To demonstrate the genetic influence in the onset of the different age-related macular disease (AMD) subtypes by analysing the genotype distribution of CFH, ARMS2, HTRA1, VEGF-A and VEGF-R polymorphisms in patients with neovascular and atrophic AMD. MATERIALS AND METHODS: The study was conducted on 101 consecutive patients with AMD diagnosis (74 exudative, 27 atrophic) following Wisconsin international classification criteria. The CFH rs1410996, ARMS2 rs10940923, VEGF-A rs833061, rs699947, and VEGF-R rs2071559 polymorphisms were analysed using real time PCR with taqman probes, and HTRA1 rs112000638 using restriction endonucleases digestion. A study was made of the genotype distribution of the different polymorphisms in our group of patients with neovascular AMD and those with the atrophic type, and a comparison was made of the results for each one of the genes studied. RESULTS: No statistically significant differences (P>.05) were found in the genotype distribution of the different polymorphisms between patients with neovascular AMD and patients with atrophic AMD in our population, although the "risk" genotypes tended to appear more frequently in patients with neovascular AMD, despite the lack of statistical significance. CONCLUSIONS: Allelic variants of CFH, ARMS2, HTRA1, VEGF-A or VEGF-R genes are not associated with the different AMD subtypes. This suggests that, although the polymorphisms seem to be associated with the disease susceptibility, they are not involved in the onset of the different clinical variants of AMD. Further studies in different populations, and with a larger cohort of patients, are needed to confirm these results.