SYSTEMIC LUPUS-ERYTHEMATOSUS - CONSIDERATIONS FOR A GENETIC APPROACH

There is powerful evidence suggesting that etiology and pathogenesis o f systemic lupus erythematosus has both genetic and environmental comp onents. Unfortunately, understanding the genetics of lupus has been im peded by knowing the pattern of inheritance. Indeed, a complex mode of inheritance for the lupus disease phenotype is suggested by the known characteristics of this disorder. Twenty-five multiplex pedigrees for lupus have been enrolled and have been used to evaluate power to reve al linkage. The power to find linkage in these pedigrees is greater fo r autosomal recessive than for autosomal dominant modes of inheritance . Once 100 similar pedigrees are available for analysis our results pr edict that linkage is likely to be present for genetic models with rel atively relaxed requirements. At loci operating by autosomal recessive inheritance linkage should be detectable despite genetic homogeneity as low as 40% and penetrance as low as 50%. For loci operating by auto somal dominant inheritance genetic homogeneity must be 60% or more whe n penetrance is as low as 50% to be able to establish linkage. Availab le preliminary data are also consistent with a possible genetic linkag e of Fc(gamma)RIII(PMN) with lupus in American Black pedigrees multipl ex for lupus.