title: Thrombocytopenia identifies a severe familial phenotype of systemic lupus erythematosus and reveals genetic linkages at 1q22 and 11p13.
abstract: Systemic lupus erythematosus (SLE) is a complicated autoimmune disease with a definite genetic predisposition. Thrombocytopenia predicts severe disease and death in SLE, making the identification of the related genetic risk factors especially important. We selected the 38 pedigrees that had an SLE patient with thrombocytopenia (platelets, < 10 x 10(9)/L [< 100,000/microL]) from a collection of 184 pedigrees multiplex for SLE. Linkages were established at 1q22-23 (maximum logarithm of odds [lod(max)] = 3.71) in the 38 pedigrees and at 11p13 (lod(max) = 5.72) in the 13 African American pedigrees. Nephritis, serositis, neuropsychiatric involvement, autoimmune hemolytic anemia, anti-double-stranded DNA, and antiphospholipid antibody were associated with thrombocytopenia. Other results show that SLE is more severe in the families with a thrombocytopenic SLE patient, whether or not thrombocytopenia in an individual patient is considered. These results are consistent with thrombocytopenia being a component of a severe familial form of SLE and with genes at 1q22-23 and 11p13 contributing to this severe phenotype and to the subsequent high mortality associated with thrombocytopenia in SLE.
authors.affiliation: Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, USA. hal-scofield@omrf.ouhsc.edu
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
authors.forename: Gail R
authors.initials: GR
authors.lastname: Bruner
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.forename: Jeff
authors.initials: J
authors.lastname: Kilpatrick
authors.forename: Debra
authors.initials: D
authors.lastname: Bacino
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
mesh_terms: D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics; D013921:Thrombocytopenia / Q000209:etiology / Q000235:genetics*