OBJECTIVE: Arthritis is a common manifestation in systemic lupus erythematosus (SLE), appearing in approximately 85% of patients. Often, the polyarthritis at presentation of SLE cannot be distinguished from rheumatoid arthritis (RA) by physical examination or history. Indeed, physicians initially tell many SLE patients that they have RA (one source of "self-reported RA"), only to have SLE established later. In addition, RA aggregates in families with an SLE proband. We predicted that pedigrees multiplex for both SLE and for self-reported RA would better isolate particular genetic effects. If this proved to be true, we would then use the increased genetic homogeneity to more easily reveal genetic linkage. METHODS: From a collection of 160 pedigrees multiplex for SLE, we selected 36 pedigrees that also contained >or=2 members with self-reported RA (19 pedigrees were African American, 14 were European American, and 3 were of other ethnic origin). Data from a genome scan of 307 microsatellite markers were evaluated for SLE linkage by contemporary genetic epidemiologic techniques. RESULTS: The most significant evidence of linkage to SLE was obtained at 5p15.3 in the European American pedigrees by both parametric (logarithm of odds [LOD] score 6.2, P = 9.3 x 10(-8)) and nonparametric (LOD score 6.9, P = 1.7 x 10(-8)) methods. The best-fitting model for this putative SLE gene in this region was a recessive gene with a population frequency of 5% and with 50% penetrance in females and 15% penetrance in males at virtually 100% homogeneity. CONCLUSION: For a genetically complex disease phenotype, an unusually powerful linkage has been found with SLE at 5p15.3 in European American pedigrees multiplex for SLE and for self-reported RA. This result predicts the presence of a gene at the top of chromosome 5 in this subset of patients that is important for the pathogenesis of SLE.
OBJECTIVE:Arthritis is a common manifestation in systemic lupus erythematosus (SLE), appearing in approximately 85% of patients. Often, the polyarthritis at presentation of SLE cannot be distinguished from rheumatoid arthritis (RA) by physical examination or history. Indeed, physicians initially tell many SLEpatients that they have RA (one source of "self-reported RA"), only to have SLE established later. In addition, RA aggregates in families with an SLE proband. We predicted that pedigrees multiplex for both SLE and for self-reported RA would better isolate particular genetic effects. If this proved to be true, we would then use the increased genetic homogeneity to more easily reveal genetic linkage. METHODS: From a collection of 160 pedigrees multiplex for SLE, we selected 36 pedigrees that also contained >or=2 members with self-reported RA (19 pedigrees were African American, 14 were European American, and 3 were of other ethnic origin). Data from a genome scan of 307 microsatellite markers were evaluated for SLE linkage by contemporary genetic epidemiologic techniques. RESULTS: The most significant evidence of linkage to SLE was obtained at 5p15.3 in the European American pedigrees by both parametric (logarithm of odds [LOD] score 6.2, P = 9.3 x 10(-8)) and nonparametric (LOD score 6.9, P = 1.7 x 10(-8)) methods. The best-fitting model for this putative SLE gene in this region was a recessive gene with a population frequency of 5% and with 50% penetrance in females and 15% penetrance in males at virtually 100% homogeneity. CONCLUSION: For a genetically complex disease phenotype, an unusually powerful linkage has been found with SLE at 5p15.3 in European American pedigrees multiplex for SLE and for self-reported RA. This result predicts the presence of a gene at the top of chromosome 5 in this subset of patients that is important for the pathogenesis of SLE.
Authors: E Rampersaud; A G Bassuk; D S Enterline; T M George; D G Siegel; E C Melvin; J Aben; J Allen; A Aylsworth; T Brei; J Bodurtha; C Buran; L E Floyd; P Hammock; B Iskandar; J Ito; J A Kessler; N Lasarsky; P Mack; J Mackey; D McLone; E Meeropol; L Mehltretter; L E Mitchell; W J Oakes; J S Nye; C Powell; K Sawin; R Stevenson; M Walker; S G West; G Worley; J R Gilbert; M C Speer Journal: J Med Genet Date: 2005-04-14 Impact factor: 6.318
Authors: Cecilia M Johansson; Renata Zunec; Mercedes A García; Hugo R Scherbarth; Guillermo A Tate; Sergio Paira; Sandra M Navarro; Carlos E Perandones; Susana Gamron; Alejandro Alvarellos; Cesar E Graf; Jorge Manni; Guillermo A Berbotto; Simon A Palatnik; Luis J Catoggio; Cristina G Battagliotti; Gian Domenico Sebastiani; Sergio Migliaresi; Mauro Galeazzi; Bernardo A Pons-Estel; Marta E Alarcón-Riquelme Journal: Hum Genet Date: 2004-07-01 Impact factor: 4.132
Authors: Samina Asad; Pernilla Nikamo; Alexandra Gyllenberg; Hedvig Bennet; Ola Hansson; Nils Wierup; Annelie Carlsson; Gun Forsander; Sten-Anders Ivarsson; Helena Larsson; Åke Lernmark; Bengt Lindblad; Johnny Ludvigsson; Claude Marcus; Kjersti S Rønningen; Jan Nerup; Flemming Pociot; Holger Luthman; Malin Fex; Ingrid Kockum Journal: PLoS One Date: 2012-05-01 Impact factor: 3.240
Authors: Prithvi Raj; Ran Song; Honglin Zhu; Linley Riediger; Dong-Jae Jun; Chaoying Liang; Carlos Arana; Bo Zhang; Yajing Gao; Benjamin E Wakeland; Igor Dozmorov; Jinchun Zhou; Jennifer A Kelly; Bernard R Lauwerys; Joel M Guthridge; Nancy J Olsen; Swapan K Nath; Chandrashekhar Pasare; Nicolai van Oers; Gary Gilkeson; Betty P Tsao; Patrick M Gaffney; Peter K Gregersen; Judith A James; Xiaoxia Zuo; David R Karp; Quan-Zhen Li; Edward K Wakeland Journal: Genome Biol Date: 2020-11-19 Impact factor: 17.906