Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Cancer Epidemiol Biomarkers Prev ; 29(1): 225-235, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31666285

RESUMEN

BACKGROUND: Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. METHODS: We performed genome-wide association studies of serum levels of AFP (N = 22,686), carcinoembryonic antigen (N = 22,309), cancer antigens 15.3 (N = 7,107), 19.9 (N = 9,945), and 125 (N = 9,824), and ALP (N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry. RESULTS: We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels. CONCLUSIONS: Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood. IMPACT: Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Niño , Preescolar , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Islandia/epidemiología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/diagnóstico , Neoplasias/genética , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Valores de Referencia , Sistema de Registros/estadística & datos numéricos , Análisis de Secuencia de ARN , Secuenciación Completa del Genoma , Adulto Joven
2.
Nat Commun ; 9(1): 4447, 2018 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-30361506

RESUMEN

Mutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidase's main subunit (gp91phox) and results in CGD. Analyzing two brothers diagnosed with CGD we identify a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1. Imputation of p.Tyr2Ter into 155K chip-genotyped Icelanders reveals six additional homozygotes, all with signs of CGD, manifesting as colitis, rare infections, or a severely impaired PMA-induced neutrophil oxidative burst. Homozygosity for p.Tyr2Ter consequently associates with inflammatory bowel disease (IBD) in Iceland (P = 8.3 × 10-8; OR = 67.6), as well as reduced height (P = 3.3 × 10-4; -8.5 cm). Overall, we find that CYBC1 deficiency results in CGD characterized by colitis and a distinct profile of infections indicative of macrophage dysfunction.


Asunto(s)
Enfermedad Granulomatosa Crónica/genética , Mutación con Pérdida de Función/genética , Niño , Colitis/genética , Colitis/patología , Citocromos b/metabolismo , Femenino , Homocigoto , Humanos , Masculino , Linaje , Estallido Respiratorio
3.
J Pediatr Surg ; 53(8): 1509-1515, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28947328

RESUMEN

BACKGROUND/PURPOSE: Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries. METHODS: Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005-2016. RESULTS: Of the 154 patients, 148 underwent portoenterostomy mostly by assigned surgical teams at median age of 64 (interquartile range 37-79) days, and 95 patients (64%) normalized their serum bilirubin concentration while living with native liver. Postoperative adjuvant medical therapy, including steroids, ursodeoxycholic acid and antibiotics was given to 137 (93%) patients. Clearance of jaundice associated with young age at surgery and favorable anatomic type of biliary atresia, whereas annual center caseload >3 patients and diagnostic protocol without routine liver biopsy predicted early performance of portoenterostomy. The cumulative 5-year native liver and overall survival estimate was 53% (95% CI 45-62) and 88% (95% CI 83-94), respectively. Portoenterostomy age <65days and annual center caseload >3 patients were predictive for long-term native liver survival, while normalization of serum bilirubin after portoenterostomy was the major predictor of both native liver and overall 5-year survival. CONCLUSIONS: The outcomes of biliary atresia in the Nordic countries compared well with previous European studies. Further improvement should be pursued by active measures to reduce patient age at portoenterostomy. RETROSPECTIVE PROGNOSIS STUDY: Level II.


Asunto(s)
Atresia Biliar/tratamiento farmacológico , Atresia Biliar/cirugía , Colestasis/tratamiento farmacológico , Colestasis/cirugía , Esteroides/uso terapéutico , Quimioterapia Adyuvante , Femenino , Humanos , Lactante , Recién Nacido , Trasplante de Hígado/métodos , Masculino , Portoenterostomía Hepática/métodos , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Países Escandinavos y Nórdicos , Resultado del Tratamiento
4.
NPJ Genom Med ; 2: 24, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29263835

RESUMEN

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10-7, 4.3 × 10-9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.

5.
Scand J Gastroenterol ; 50(11): 1368-75, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25979112

RESUMEN

OBJECTIVE: We analyzed the incidence of inflammatory bowel disease (IBD) in Iceland for the period 1995-2009. MATERIAL AND METHODS: New cases of ulcerative colitis (UC) and Crohn's disease (CD) were retrieved by thorough review of all small and large intestinal pathology reports with any type of inflammation from all the pathology departments in Iceland for the period 1995-2009. All suspicious new cases of IBD were then scrutinized retrospectively by examination of their clinical records. RESULTS: A total of 1175 cases of IBD were diagnosed, 884 UC, 279 CD and 12 IBD unclassified. The crude annual incidence of UC was 20.5/100,000, increasing from 18.1 the first 5-year period to 22.1 the last 5-year period. The crude annual incidence of CD was 6.5/100,000, 6.7 the first 5-year period and 6.6 the last 5-year period. CONCLUSIONS: This study shows statistically significant increase in the incidence of UC during the study period. The incidence of CD has however remained stable.


Asunto(s)
Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Islandia/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Proyectos de Investigación , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
6.
Scand J Gastroenterol ; 48(12): 1399-404, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24164345

RESUMEN

AIM AND BACKGROUND. We describe the changes in incidence and disease location of inflammatory bowel disease (IBD) in children in one country over six decades. Iceland is an island with centralized health information. Children with IBD are cared for in only two hospitals. Iceland is therefore well suited for nationwide epidemiologic studies. MATERIAL AND METHODS. All IBD patients 16 years and younger diagnosed in Iceland from 1950-2010 were included. Patients were identified retrospectively from 1950-1989, and prospectively from 1990-2010, by reviewing pathology and charts for all patients diagnosed with IBD. Criteria for the diagnosis of ulcerative colitis (UC) were history of blood in stools for >3 weeks, characteristic endoscopic appearance of continuous inflammation of the colon, and histologic appearance of acute and chronic inflammation of the colon without granulomata. Criteria of Crohn's disease (CD) were history of abdominal pain, blood in stools, and endoscopic, radiologic, and histologic features of CD. RESULTS. One hundred and ten children were diagnosed with IBD, 61 with UC, 44 with CD, and 5 with indeterminate disease. The median age was 13.7 ± 2.6, with sex distribution varying from decade to decade. From 1980 until 2000, there was a dramatic increase in the incidence of IBD from 1.2 per 100,000 children <16 years of age to 5.6 per 100,000. However, in the past decade, the incidence has plateaued. CONCLUSION. In this population-based pediatric study, we report an increase in the incidence of IBD from 1950-2000. Incidence in Icelandic children is lower than in published studies from other Northern European countries.


Asunto(s)
Enfermedades Inflamatorias del Intestino/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Humanos , Islandia/epidemiología , Incidencia , Lactante , Modelos Lineales , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Distribución por Sexo
7.
Laeknabladid ; 97(9): 477-80, 2011 09.
Artículo en Islandés | MEDLINE | ID: mdl-21911908

RESUMEN

Vitamin D is necessary for normal bone growth. Deficiency of vitamin D can lead to rickets in children and osteomalacia in adults. It is difficult to reach the recommended daily dose of vitamin D in children without cod liver oil or other vitamin D supplementation. Several cases of rickets have been diagnosed in Iceland the past few years. Studies suggest a worldwide increase in the prevalence of the disorder. We report on a girl who was diagnosed with rickets at the age of 27 months. She received inadequate amounts of vitamin D supplementation in the form of AD drops and cod liver oil. Because of food allergy she was on a restricted diet which limited her intake of dietary vitamin D. After diagnosis, she received a high-dose vitamin D therapy (Stoss therapy) which corrected the deficiency. Key words: rickets, food allergy, vitamin D.


Asunto(s)
Suplementos Dietéticos , Raquitismo/tratamiento farmacológico , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/administración & dosificación , Vitaminas/administración & dosificación , Preescolar , Aceite de Hígado de Bacalao/administración & dosificación , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/dietoterapia , Humanos , Política Nutricional , Radiografía , Raquitismo/diagnóstico por imagen , Raquitismo/etiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/diagnóstico
8.
Arthritis Rheum ; 56(8): 2633-9, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17665420

RESUMEN

OBJECTIVE: Patients with ankylosing spondylitis (AS) and approximately 50% of their first-degree relatives may have a genetic abnormality that results in subclinical intestinal inflammation. This study was undertaken to examine the familial occurrence and cosegregation of AS and inflammatory bowel disease (IBD) in order to determine whether there is a shared genetic risk factor in families. METHODS: The Icelandic genealogy database and population-wide data on all living Icelanders diagnosed as having AS (n = 205) and/or IBD (n = 1,352) were used to estimate the risk ratios of AS for relatives of patients with AS, the risk ratios of IBD for relatives of patients with IBD, and the cross-risk ratios of AS for relatives of patients with IBD or of IBD for relatives of patients with AS. The mean kinship coefficients for each disease were calculated. The control population for disease risk calculations comprised 10,000-100,000 sets of matched Icelandic subjects. RESULTS: First-, second-, and third-degree relatives of patients with AS had risk ratios of 94, 25, and 3.5, respectively, indicating an increased risk of developing AS (each P < 0.0005), while first-, second-, and third-degree relatives of patients with IBD had risk ratios for IBD of 4.4, 2.2, and 1.4, respectively (each P < 0.0001). The cross-risk ratios of IBD were 3.0 and 2.1 in first- and second-degree relatives of patients with AS, respectively, and were the same for AS in first- and second-degree relatives of patients with IBD. With the exception of Crohn's disease, the risk of having AS, ulcerative colitis, or IBD in spouses of patients with these diseases did not differ significantly from that in controls. Calculation of the kinship coefficients confirmed these patterns of familial risk. CONCLUSION: Patients with AS or IBD in Iceland are significantly more related to each other than are randomly sampled control subjects, in terms of an increased risk of either or both conditions developing in third-degree relatives. These findings suggest that one or more undiscovered genetic variants may underlie the risk of both diseases.


Asunto(s)
Salud de la Familia , Predisposición Genética a la Enfermedad , Enfermedades Inflamatorias del Intestino/genética , Linaje , Espondilitis Anquilosante/genética , Femenino , Humanos , Islandia/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/patología , Masculino , Epidemiología Molecular/métodos , Oportunidad Relativa , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/patología
9.
Clin Gastroenterol Hepatol ; 2(9): 806-12, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15354281

RESUMEN

BACKGROUND AND AIMS: Both genetic and environmental factors play a role in the development of Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD). The aim of this study was to estimate the genetic component in IBD in Iceland. METHODS: A population-based sample, representing everyone diagnosed with IBD in Iceland from 1950 to 1996, was studied using a computerized population-wide genealogic database. The relationships among the patients were analyzed by calculating the kinship coefficient and the relative risk. RESULTS: The kinship coefficients for the patients were significantly greater than the mean kinship coefficient for the controls ( P < 10 -6 ). The risk ratio for siblings of IBD, UC, and CD patients was 5.0 ( P < 0.001), 5.9 ( P < 0.001), and 4.1 ( P = 0.033), respectively. The cross-risk ratio for siblings of UC patients developing CD (or vice versa) was 2.6 ( P = 0.015). CONCLUSIONS: The results indicate that the IBD patients are more closely related than the controls, which strongly supports the involvement of a genetic component in the development of IBD in Icelandic patients. We find that the increase in risk for relatives of UC probands to develop UC, or relatives of CD probands to develop CD, is greater than the increase in risk for relatives of UC probands to develop CD, or relatives of CD probands to develop UC.


Asunto(s)
Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Femenino , Genealogía y Heráldica , Humanos , Islandia , Masculino , Oportunidad Relativa , Linaje
10.
Dig Dis Sci ; 47(5): 1122-8, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12018911

RESUMEN

The aim of this study was to determine the nationwide incidence of collagenous and lymphocytic colitis in Iceland and the location of histopathological changes in the large bowel. All pathology reports of patients diagnosed with or suspected of having collagenous colitis or lymphocytic colitis in the period 1995-1999 were identified. All pathology samples were reevaluated using strict diagnostic criteria. After reevaluation 125 patients fulfilled our diagnostic criteria, 71 as collagenous colitis and 54 as lymphocytic colitis. The mean annual incidence for collagenous colitis was 5.2/100,000 inhabitants, and the mean age at diagnosis was 66.1 years. The mean annual incidence for lymphocytic colitis was 4.0/100,000 inhabitants, the mean age at diagnosis was 68.7 years. Both diseases more commonly involved the colon than the rectum. The incidence of collagenous colitis and lymphocytic colitis is high in Iceland. The mean annual incidence of collagenous colitis is much higher in Iceland than hitherto reported elsewhere.


Asunto(s)
Colitis/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Colitis/patología , Colágeno , Colon/patología , Femenino , Humanos , Islandia/epidemiología , Linfocitosis , Masculino , Persona de Mediana Edad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...