RESUMO
Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21-22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.
Assuntos
Hibridização Genômica Comparativa , Dermatite Atópica/genética , Estudo de Associação Genômica Ampla , Psoríase/genética , Alelos , Estudos de Casos e Controles , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 6/genética , Estudos de Coortes , Loci Gênicos , Humanos , Modelos Logísticos , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único , Controle de Qualidade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Atopic dermatitis (AD) is characterized by epidermal barrier failure and immune-mediated inflammation. Evidence on AD as a potential risk factor for inflammatory comorbidities is scarce. OBJECTIVES: We sought to test the hypothesis that prevalent AD is a risk factor for incident rheumatoid arthritis (RA) and inflammatory bowel disease (IBD; Crohn disease [CD], ulcerative colitis [UC]) and is inversely related to type 1 diabetes (T1D) and to investigate established RA, IBD, and T1D susceptibility loci in AD. METHODS: This cohort study used data from German National Health Insurance beneficiaries aged 40 years or younger (n = 655,815) from 2005 through 2011. Prevalent AD in the period 2005 to 2006 was defined as primary exposure, and incident RA, IBD, and T1D in the period 2007 to 2011 were defined as primary outcomes. Risk ratios were calculated with generalized linear models. Established RA, IBD, and T1D loci were explored in high-density genotyping data from 2,425 cases with AD and 5,449 controls. RESULTS: Patients with AD (n = 49,847) were at increased risk for incident RA (risk ratio [RR], 1.72; 95% CI, 1.25-2.37) and/or IBD (CD: RR, 1.34; 95% CI, 1.11-1.61; UC: RR, 1.25; 95% CI, 1.03-1.53). After adjusting for health care utilization, there was a nominally significant inverse effect on T1D risk (RR, 0.72; 95% CI, 0.53-0.998). There was no disproportionate occurrence of known RA, CD, UC, or T1D risk alleles in AD. CONCLUSIONS: AD is a risk factor for the development of RA and IBD. This excess comorbidity cannot be attributed to major known IBD and RA genetic risk factors.
Assuntos
Artrite Reumatoide/epidemiologia , Dermatite Atópica/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Razão de Chances , Prevalência , Fatores de Risco , Adulto JovemRESUMO
The purpose of this descriptive comparative survey was to examine differences in family resiliency between hemodialysis patients and caregivers across three ethnically diverse samples that included Anglo-Americans, Mexican Americans, and South Koreans. The study was based on the Family Resiliency Model developed by McCubbin, Thompson, and McCubbin. The patients were in end-stage renal disease and were receiving hemodialysis treatments at either a freestanding hemodialysis unit or a 30-bed dialysis hospital unit. South Korean patients on hemodialysis and their caregivers perceived the stressors imposed by their illness to be significantly greater than either of the other ethnic groups, and they also scored lower on the resiliency measure than the other two groups. Findings of the study support the need to understand the dynamics of family resiliency from a cultural perspective.