Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1832526 (PCC)
 5,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.
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PMID:Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients. 1973 89

Three important factors, including genetics, environment factors and autoimmunity play a role in the pathogenesis of rheumatoid arthritis (RA). The heritability of RA has been accounted to be 50-60%, while the HLA involvement in heritability of the disease has been accounted to be 10-40%. It has been documented that shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, some HLA alleles like HLA-DRB1*13 and DRB1*15 are connected to RA susceptibility. An advanced classification of SE categorizes SE alleles into four main groups namely, S1, S2, S3D, and S3P. The S2 and S3P groups have been linked to susceptibility of seropositive RA. Various genome-wide association studies (GWAS) have discovered many susceptibility loci implicated in pathogenesis of RA. Some of the important single nucleotide polymorphisms (SNPs) linked to RA are TRAF1, STAT4, CTLA4, IRF5, CCR6, PTPN22, IL23R, and PADI4. HLA and non-HLA genes may discriminate anti-cyclic citrullinated peptide (anti-CCP) antibody-positive and anti-CCP-negative RA groups. Furthermore, risk of the disease has also been linked to environmental agents, mainly cigarette smoking. Pharmacogenomics has also confirmed SNPs or genetic patterns that might be linked to drugs responses. Different aspects of genetic involvement in the pathogenesis, etiology, and RA complications are reviewed in this article.
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PMID:Genetic implications in the pathogenesis of rheumatoid arthritis; an updated review. 3090 15