Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemolytic anemia is a forme fruste of systemic lupus erythematosus (SLE), being observed months or even years before the onset of other clinical manifestations in some patients. We hypothesized that hemolytic anemia in those SLE-affected patients would identify a group of SLE pedigrees that share a high degree of genetic homogeneity. From 160 multiplex SLE pedigrees, we sought evidence for linkage in 35 (16 African-American, 17 European-American, and 2 Hispanic) who had at least one SLE-affected patient with hemolytic anemia. Significant linkage was present at 11q14 in the 16 African-American pedigrees, yielding a maximum two-point logarithm of odds (LOD) score of 4.5 at D11S2002. The segregation pattern of SLE in these African-American pedigrees suggested a dominant mode of inheritance and, when maximized across penetrance and disease allele frequencies, produced a multipoint LOD of 4.7. Multipoint analysis yielded a multipoint heterogeneity LOD score of 3.6 (alpha = 0.63), again with maximum LOD at D11S2002. Finally, markers typed 7 centimorgans to either side of D11S2002 achieved LOD scores of 3 or better by using the maximized model, supporting linkage to 11q14. Clearly, pedigree ascertainment based on select clinical manifestations is an important tool, capable of revealing otherwise cryptic genetic linkages in complex genetic diseases. Thus, we show strong evidence for an SLE susceptibility gene, SLEH1, near D11S2002 in African-American pedigrees multiplex for SLE that have at least one SLE-affected patient with hemolytic anemia.
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PMID:Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemia. 1219 84

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex genetics. We evaluated pedigrees multiplex for SLE that had an affected with antinucleolar antibodies to increase the homogeneity for genetic linkage analysis. We found a significant linkage effect on chromosome 11q14 at marker D11S2002 in African-American Pedigrees. This effect produced a maximum LOD score of 5.62 using a dominant inheritance model with 95% penetrance in males and 99% penetrance in females. The results were supported by multipoint linkage analysis. Fine mapping of the region with two additional markers within 6 cM of D11S2002 further provided evidence of linkage in this region. Linkage at D11S2002, named SLEH1, was previously found in some of these same African-American pedigrees multiplex for SLE, but who were stratified by hemolytic anemia (Kelly et al, submitted). In conclusion, an important SLE susceptibility gene, SLEH1 at 11q14, is identified in African-Americans when stratifying pedigrees by antinucleolar autoantibodies.
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PMID:Genetic linkage of systemic lupus erythematosus with chromosome 11q14 (SLEH1) in African-American families stratified by a nucleolar antinuclear antibody pattern. 1221 99