RESUMEN
Clinical and molecular studies implicate tumor necrosis factor alpha (TNF-alpha) as a key mediator in the initiation and propagation of Crohn disease (CD). Genetic associations have been documented between promoter polymorphisms of TNF-alpha and CD; however, these associations have not been universally replicated. In this study, we set out to examine the association of five promoter TNF-alpha polymorphisms in CD subjects from a founder population. In total, 128 CD subjects and 103 ethnically matched healthy controls were genotyped with time-of-flight mass spectrometry for the following five single nucleotide polymorphisms (SNPs) in the 5' flanking region of TNF-alpha gene: -1031 (T-->C), -863 (C-->A), -857 (C-->T), -308 (G-->A), and -238 (G-->A). Primer sequences, termination mixes, and multiplexing were determined with Sequenom SpectroDESIGNER software v1.3.4. The minor allele frequency for the TNF-alpha SNPs in subjects with CD and healthy controls, respectively, were -238 (5.5% vs. 5.3%); -308 (17.6% vs. 18.9%); -857 (5.1% vs. 7.8%); -863 (19.1% vs. 17.5%), and -1031 (24.6% vs. 22.8%). Thus, none of the TNF-alpha variants was associated with CD. Furthermore, no genotype/phenotype correlations were observed for the mutant allele of the TNF-alpha variants and selected clinical outcomes. In conclusion, there was no significant association for any of the TNF-alpha promoter polymorphism tested and CD in the Newfoundland population.
Asunto(s)
Enfermedad de Crohn/genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/genética , Enfermedad de Crohn/etiología , Cartilla de ADN/genética , Humanos , Terranova y LabradorRESUMEN
Crohn's disease (CD) is an inflammatory bowel disease that is likely the result of an interplay of genetic and environmental factors. Recent studies have postulated similarities in genetic susceptibility of CD and psoriasis. Because the +39604 SEEK1 polymorphism in chromosome 6p has recently been associated with psoriasis, the prevalence of this polymorphism, as well as two additional single nucleotide polymorphisms in the SEEK1 gene, in patients with CD from the Newfoundland population were determined. In total, 126 CD and 105 ethnically matched healthy controls were genotyped via time-of-flight mass spectrometry for the following SEEK1 polymorphisms: +39604 and +39709 in exon 2 and +26680 in exon 5. The allele frequency for the mutant allele for +39604, +39709, and +26680 was 16.3%, 44.5%, and 0%, respectively, in subjects with CD as compared with 17.6%, 42.0%, and 0%, respectively, in controls. There was no statistical difference in any of the variants between patients with CD and controls. The SEEK1polymorphisms +39604, +39709, and +26680 are not associated with CD in the Newfoundland population.
Asunto(s)
Enfermedad de Crohn/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas/genética , Adulto , ADN/química , ADN/genética , ADN/aislamiento & purificación , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes/genética , Genotipo , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Terranova y Labrador , Reacción en Cadena de la PolimerasaRESUMEN
This study sought to quantify the familial risk of preeclampsia (proteinuric hypertension) in Newfoundland and to identify characteristics in probands that predict increased familial risk. Reviewed were 5173 obstetric charts from 10 hospitals, representing 99% of deliveries on the island of Newfoundland for a 1-yr period from April 1996 to March 1997; pregnancy-induced hypertension was diagnosed according to strict criteria. Family obstetric histories were obtained from identified probands with preeclampsia, and sisters and mothers of probands were interviewed. In addition, the obstetric charts from sisters and mothers were reviewed to identify preeclampsia. The incidence of preeclampsia in the population was 5.6% (n = 292), and in primiparous women it was 7.9%. Factors independently associated with increased risk of preeclampsia included primiparous delivery, multiple gestation, pregestational and gestational diabetes, maternal age of more than 35 yr, and region of the province. Of 330 sisters identified, 217 had 445 pregnancies, with 331 charts located for review. The incidence of preeclampsia (based on chart review) in 163 primiparous sisters was 20.2%. The relative risk of preeclampsia in primiparous sisters of probands with preeclampsia compared with primiparous women in the population was 2.6 (95% confidence interval, 1.8 to 3.6). Factors in probands independently associated with a higher risk of preeclampsia in sisters included at least 2+ proteinuria and region of the province. This population-based study, which used unbiased ascertainment and strict diagnostic criteria, demonstrated a significantly higher risk of preeclampsia in sisters of probands with preeclampsia, particularly when probands were defined by severity of preeclampsia and by geographic region.
