Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic factors seem to play a significant role in susceptibility to systemic lupus erythematosus (SLE). We previously described the amino acid polymorphism (Val14Met) within the IFN-gamma receptor 1 (IFN-gammaRI), and that the frequency of the Metl4 allele in SLE patients was significantly higher than that of the healthy control population [Tanaka et al. (1999) Immunogenetics 49, 266-271]. We also found an amino acid polymorphism (Gln64Arg) within IFN-gamma receptor 2 (IFN-gammaR2). Since the IFN-gamma receptor is a complex consisting of IFN-gammaR1 and IFN-gammaR2, we searched for the particular combination of two kinds of amino acid polymorphisms found within the IFN-gamma receptor which plays a prominent role in susceptibility to SLE. The greatest risk of the development of SLE was detected in the individuals who had the combination of IFNGR1 Met14/Val14 genotype and IFNGR2 Gln64/Gln64 genotype.
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PMID:The combination of polymorphisms within interferon-gamma receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus. 1040

Genetic polymorphism is a difference in DNA sequence among individuals, groups, or populations that give rise to different forms. Differences in DNA sequences that occur naturally in a population. Single nucleotide substitutions, insertions and deletions of nucleotides and repetitive sequences (microsatellites) are all examples of polymorphism. The position at which such a sequence difference is found is a polymorphic site. A single nucleotide substitution is called a single nucleotide polymorphism (SNP). SNPs can occur in coding parts of the gene. If they result in genetic code change, amino-acid polymorphism would occur. The heterodimeric IFN-gamma receptor (IFNGR) complex was made up of two receptor subunits including IFNGR-1 and IFNGR-2. There exist five dbSNP alleles in IFNGR1 exon region and six dbSNP alleles in IFNGR2. Some researchers had found that the greatest risk of the development of systemic lupus erythematosus (SLE) be detected in the individuals who had the Met14/Val14 genotype or the combination of IFNGR1 Met14/Val14 genotype and IFNGR2 Gln64/Gln64 genotype in Japanese patients. So we aimed to assess the association between two polymorphisms within the IFNGR gene (A88G and A839G) and SLE in Chinese patients. This study included 154 patients with SLE and 159 unrelated healthy controls. We examined the IFNGR genotype by the reverse transcription-polymerase chain reaction (RT-PCR)-single-strand conformation polymorphism method, RT-PCR-restriction fragment length polymorphism method and DNA sequencing. Genotype frequencies between SLE patients and controls were compared and relationship between genotype frequencies and clinical manifestations of SLE were evaluated. We found that IFNGR2 Arg64/Arg64 genotype decrease the risk of SLE (OR = 2.326, 95% CI 1.181-4.581, Fisher P = 0.015), and the same as IFNGR2 Arg64/Arg64 genotype and IFNGR1 Val14/Val14 genotype combination (OR = 2.420, 95% CI 1.206-4.854, Fisher P = 0.013). The allelic frequency of Val14/Met14 is significantly higher in the patients with oral ulcer or thrombocytopenia when compared with patient without these clinical feature (OR = 4.630, 95% CI 1.370-15.640, Fisher P = 0.021; or OR = 6.368, 95% CI 2.009-20.191, Fisher P = 0.003). On the contrary, the allelic frequency of Val14/Val14 is lower in the patients with oral ulcer or thrombocytopenia than those without these clinical feature (OR = 0.216, 95% CI 0.064-0.730, Fisher P = 0.021; or OR = 0.157, 95% CI 0.050-0.498, Fisher P = 0.003). And after data analysis, we also find that the allelic frequency of Gln64/Gln64 is lower in the patients with arthritis when compared with patient without arthritis (OR = 0.369, 95% CI 0.166-0.818, Fisher P = 0.017). We can conclude that the IFNGR polymorphisms (Val14Met and Gln64Arg) are protective in SLE in Chinese patients. We describe a novel association between Val14/Met14 carriage and patients with oral ulcer or thrombocytopenia.
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PMID:The interferon-gamma receptor gene polymorphisms (Val14Met and Gln64Arg) are not associated with systemic lupus erythematosus in Chinese patients. 1761 44

In recent years, compelling evidence has been gathered that supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). Different blood cell populations of SLE patients are characterized by a global loss of DNA methylation. This process is associated with defects in ERK pathway signalling and consequent DNMT 1 downregulation. Hypomethylation of gene promoters has been described, which permits transcriptional activation and therefore functional changes in the cells and also hypomethylation of the ribosomal RNA gene cluster. Among the identified targets undergoing demethylation are genes involved in autoreactivity (ITGAL), osmotic lysis and apoptosis (PRF1, MMP14 and LCN2), antigen presentation (CSF3R), inflammation(MMP 14), B- T-cell interaction (CD70 and CD40LG) and cytokine pathways (CSF3R, IL-4, IL-6 and IFNGR2). DNA methylation inhibitors are also known to induce autoreactivity in vitro and cause a lupus-like disease in vivo. Further, altered patterns of histone modifications have been described in SLE. CD4+ lymphocytes undergo global histone H3 and H4 deacetylation and consequent skewed gene expression. Although multiple lines of evidence highlight the contribution of epigenetic alterations to the pathogenesis of lupus in genetically predisposed individuals, many questions remain to be answered. Attaining a deeper understanding of these matters will create opportunities in the promising area of epigenetic treatments.
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PMID:A new epigenetic challenge: systemic lupus erythematosus. 2162 46