RESUMO
The Fc-α receptor (FcαR/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis. No such difference was found in 42 patients with other renal diseases. The patients with IgAN without disease progression had stable but high levels of sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89 in the disease progression group. Moreover, levels of sCD89 complexes were correlated with one of the five CD89 genetic variants in 212 patients with IgAN and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377 was significantly associated with a lower expression of sCD89. However, no association between CD89 gene polymorphisms and susceptibility to IgAN was detected. Thus, we found an association between the levels of sCD89-IgA complexes in serum and the severity of IgAN, and a possible genetic component in regulating the production or expression of sCD89.
Assuntos
Antígenos CD/sangue , Antígenos CD/genética , Progressão da Doença , Predisposição Genética para Doença/genética , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/genética , Receptores Fc/sangue , Receptores Fc/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo Antígeno-Anticorpo/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Imunoglobulina A/metabolismo , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: IgA nephropathy (IgAN) and nephritis in Systemic Lupus Erythematosus (SLE) are two common forms of glomerulonephritis in which genetic findings are of importance for disease development. We have recently reported an association of IgAN with variants of TGFB1. In several autoimmune diseases, particularly in SLE, IRF5, STAT4 genes and TRAF1-C5 locus have been shown to be important candidate genes. The aim of this study was to compare genetic variants from the TGFB1, IRF5, STAT4 genes and TRAF1-C5 locus with susceptibility to IgAN and lupus nephritis in two Swedish cohorts. PATIENTS AND METHODS: We genotyped 13 single nucleotide polymorphisms (SNPs) in four genetic loci in 1252 DNA samples from patients with biopsy proven IgAN or with SLE (with and without nephritis) and healthy age- and sex-matched controls from the same population in Sweden. RESULTS: Genotype and allelic frequencies for SNPs from selected genes did not differ significantly between lupus nephritis patients and SLE patients without nephritis. In addition, haplotype analysis for seven selected SNPs did not reveal a difference for the SLE patient groups with and without nephritis. Moreover, none of these SPNs showed a significant difference between IgAN patients and healthy controls. IRF5 and STAT4 variants remained significantly different between SLE cases and healthy controls. In addition, the data did not show an association of TRAF1-C5 polymorphism with susceptibility to SLE in this Swedish population. CONCLUSION: Our data do not support an overlap in genetic susceptibility between patients with IgAN or SLE and reveal no specific importance of SLE associated SNPs for the presence of lupus nephritis.
Assuntos
Predisposição Genética para Doença , Glomerulonefrite por IGA/genética , Nefrite Lúpica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , Fatores Reguladores de Interferon/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fator de Transcrição STAT4/genética , Fator 1 Associado a Receptor de TNF/genética , Fator de Crescimento Transformador beta1/genética , Adulto JovemRESUMO
BACKGROUND: There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis. METHODS: We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden. RESULTS: Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P Assuntos
Variação Genética
, Glomerulonefrite por IGA/genética
, Fator de Crescimento Transformador beta1/genética
, Adolescente
, Adulto
, Idoso
, Feminino
, Predisposição Genética para Doença
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Polimorfismo de Nucleotídeo Único
, Adulto Jovem
