Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemia

被引:30
作者
Kelly, JA
Thompson, K
Kilpatrick, J
Lam, T
Nath, SK
Gray-McGuire, C
Reid, J
Namjou, B
Aston, CE
Bruner, GR
Scofield, RH
Harley, JB
机构
[1] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA
[2] Case Western Reserve Univ, Cleveland, OH 44106 USA
[3] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA
[4] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA
关键词
D O I
10.1073/pnas.182162399
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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, markerstyped 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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页码:11766 / 11771
页数:6
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