RESUMO
Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.
Assuntos
Povo Asiático/genética , Dermatite Atópica/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Estudos de Casos e Controles , China/epidemiologia , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 5/genética , Dermatite Atópica/epidemiologia , Proteínas Filagrinas , Humanos , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Fatores de RiscoRESUMO
INTRODUCTION: Assessment of brain tumor proliferative potential provides important prognostic information that supplements standard histopathologic grading. Proton magnetic resonance spectroscopy ((1)H-MRS) gives completely different information, relating to cell membrane proliferation, neuronal damage, energy metabolism and necrotic transformation of brain or tumor tissues. The aim of this study was to investigate the relationship between (1)H-MRS and tumor proliferative potential in astrocytomas. METHODS: We studied 34 patients with histologically verified astrocytomas using the (1)H-MRS protocol following routine MRI preoperatively. The tumor in 26 of these patients was classified as grade I/II (low grade), and the tumor in the remaining patients as grade III/IV (high grade) according to the World Health Organization classification criteria of nervous system tumors (2000). The tumor in 21 patients was homogeneous astrocytoma, and of these 17 were classified as low grade and 4 as high grade. Expression of proliferating cell nuclear antigen (PCNA) was determined immunohistochemically using streptavidin-biotin-peroxidase complex (SP) staining. RESULTS: The ratios of choline (Cho) to N-acetylaspartate (NAA) and Cho to creatine (Cr) in those with high-grade astrocytomas (n=4) were significantly higher than in those with low-grade astrocytomas (n=17) (t=2.899, P=0.009; t=3.96, P=0.001, respectively), and were found to be significantly correlated with the expression of PCNA in 21 patients with homogeneous astrocytomas (r=0.455, P=0.038; r=0.633, P=0.002, respectively). CONCLUSIONS: We conclude that (1)H-MRS may be a valuable method for predicting preoperatively the degree of malignancy of homogeneous astrocytomas by enabling the calculation of the Cho/NAA and Cho/Cr ratios in vivo, and indirect evaluation of the tumor proliferative potential and prognosis, which are not available using conventional magnetic resonance imaging (MRI).