title: [The molecular genetics of rheumatoid arthritis disease gene].
abstract: Rheumatoid arthritis(RA) is a chronic polyarthritis of unknown etiology affecting approximately 1% of the population worldwide. Previous studies have shown that the ratio of the risk for siblings of patients with the disease versus the prevalence of that disease in the general population (lambda s) is much greater in RA, suggesting that genetic factors may be involved in familial clustering. Using microsatellite marker analysis and sib-pair linkage study, we have identified three chromosome regions D1S214/253, D8S556 and DXS1232/984 as candidate loci for RA disease genes. In this article, we review the molecular genetic findings on the RA disease genes located respectively at each of the above chromosome regions. We show that the death receptor 3(DR3) gene, a Fas family member, containing nucleotide polymorphism is the candidate disease gene located at D1S214/253. We also identify the mutant forms of angiopoietin-1(Ang-1) and Dbl proto-oncogenes respectively as the candidate genes located at D8S556 and DXS1232/984. We surmise that these mutations are responsible for the impairment of apoptosis induction, angiogenesis and leukocyte function in the patients, which may predispose to autoimmunity.
authors.affiliation: Department of Rheumatology, Kobe University FSH School of Medicine.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shiozawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Komai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Masae
authors.initials: M
authors.lastname: Sato
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nakatsukasa
authors.forename: Toshie
authors.initials: T
authors.lastname: Nakashima
authors.forename: Rie
authors.initials: R
authors.lastname: Okayama
authors.forename: China
authors.initials: C
authors.lastname: Sakai
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000235:genetics; D042683:Angiopoietin-1; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity; D002878:Chromosomes, Human, Pair 1; D020022:Genetic Predisposition to Disease; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D011110:Polymorphism, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D053219:Receptors, Tumor Necrosis Factor, Member 25
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human