RESUMO
BACKGROUND: Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. METHODS: We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-ß) in 1326 unrelated subjects comprising of healthy controls (nâ¯=â¯464), type 2 diabetics with nephropathy (DN, nâ¯=â¯448) and type 2 diabetes without nephropathy (T2D, nâ¯=â¯414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). RESULTS: Individual SNP analysis showed highest association of IL-1ß rs16944-TT genotype (ORâ¯=â¯3.51, 95%CIâ¯=â¯2.36-5.21, Pâ¯=â¯0.001) and TNF-α rs1800629-AA genotype (ORâ¯=â¯2.75, 95% CIâ¯=â¯1.64-4.59, Pâ¯=â¯0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (ORâ¯=â¯4.25, 95%CIâ¯=â¯3.3-14.20, Pâ¯=â¯0.0016) and GACGACCTT (ORâ¯=â¯21.3, 95%CIâ¯=â¯15.1-28.33, Pâ¯=â¯0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-foldâ¯=â¯4.43⯱â¯1.11) in DN. TNF-α, IL-6 and IL-1ß transcript levels were significantly modulated by promoter region SNPs. CONCLUSIONS: The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1ß gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects.
Assuntos
Nefropatias Diabéticas/genética , Inflamação/genética , Interleucina-1beta/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Idoso , Estudos de Casos e Controles , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin's lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect.
RESUMO
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