{ "id": "112ce6bc-992a-4795-8ca5-775bfbf4712a", "disease": { "id": "H00630", "names": [ "Rheumatoid arthritis" ], "dbLinks": { "icd10": [ "M05" ], "mesh": [ "D001172" ] }, "category": "Immune system disease", "description": "Rheumatoid arthritis (RA) is a common autoimmune disease that primarily manifests as chronic inflammatory arthropathy. Persistent synovitis leads to cartilage destruction, bone erosions and periarticular decalcification, subsequently resulting in impaired joint function. It is more common between the ages of 35 and 50 years, affecting three times more women than men. Susceptibility to RA is genetically determined with multiple genes contributing. Inheritance of HLA DRB1 alleles encoding a distinctive five-amino-acid sequence known as the \"shared epitope\" (SE) is the best characterized genetic risk factor. The mechanism by which the SE alleles contribute to the development of RA is not very clear. It has been postulated that the presence of these conserved sequences in the antigen-binding groove alters the way antigenic peptides are bound to and presented to T-cell lymphocytes. This, in turn, may trigger abnormal immune responses and lead to RA." }, "article": { "id": "23897126", "text": "OBJECTIVE:\nTo estimate familial aggregation of rheumatoid arthritis (RA) in 3 large population-representative samples and to test if familial aggregation is affected by rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) status, type of relative, sex, and age at onset of RA.\n\nMETHODS:\nA register-based nested case-control study was performed in the Swedish total population. Data on patients with RA were ascertained through the nationwide Swedish Patient Register (n = 88,639), the clinical Swedish Rheumatology Quality Register (n = 11,519), and the Epidemiological Investigation of Rheumatoid Arthritis case-control study (n = 2,871). Data on first- and second-degree relatives were obtained through the Swedish Multigeneration Register. Familial risks were calculated using conditional logistic regression.\n\nRESULTS:\nConsistent across data sources, the familial odds ratio for RA was ∼3 in first-degree relatives of RA patients and 2 in second-degree relatives. Familial risks were similar among siblings, parents, and offspring. Familial aggregation was not modified by sex, but was higher in RA patients with early-onset disease and in RF/ACPA-positive RA patients. The observed familial risks were consistent with a heritability of ∼50% for ACPA-positive RA and ∼20% for ACPA-negative RA.\n\nCONCLUSION:\nThe pattern of risks suggests that familial factors influence RA in men and women equally and that these factors are of less importance for late-onset RA. Familial factors are more important for seropositive RA, but there is significant familial overlap between seropositive RA and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest that heritability of RA is lower than previously reported, in particular for ACPA-negative RA." }, "questions": [ { "id": "493c4671-e046-4f87-b7c0-cb9cd58b98c9", "text": "What are the risk factors of Rheumatoid arthritis?", "answers": [ { "answer_start": 23, "text": "familial aggregation" }, { "answer_start": 1200, "text": "familial risks" }, { "answer_start": 981, "text": "Familial risks were similar among siblings, parents, and offspring" } ] } ] }