There's no germ for psoriasis, but there is a gene, and its discovery isimminent. Like many other diseases (See the asthma/hay fever story, p.1.), psoriasis clearly runs in families. About 30 percent of psoriasispatients have an affected first-degree relative.By combing the DNA of selected large families with many afflictedmembers, researchers at the University of Texas Southwest MedicalCenter in Dallas have identified telltale markers that point to thesusceptibility factor's precise location. Their report in the May 20 issueof Science, is titled, "Gene for Familial Psoriasis SusceptibilityMapped to the Distal End of Human Chromosome 17q.""To track down the putative mutated gene that inflames the skin cellsof its victims, the Texans conducted a genome-wide linkage analysis,with polymorphic microsatellites (stuttering DNA bases), in eightfamilies from 15 states, containing 151 members, of whom 65 had thedisease.As a senior author of the paper, Anne Bowcock, told BioWorld Today,"we were hoping to find DNA markers that would co-segregate with apsoriasis susceptibility locus in these families."One of the biggest kindreds showed a very high statistical linkage nearthe tip of chromosome 17's long arm. In the other pedigrees, thislinkage ran from 25 to 50 percent in the same chromosomal region."This is evidence that psoriasis can be familial, and we have localizedits gene or genes," Bowcock said, adding, "So now what we want to dois go after that gene."No Link To HLA ComplexA negative finding also proved useful. For a long time, immunologistshave speculated that the trigger for psoriasis, an autoimmune disease,lurks in the human leukocyte antigen (HLA) complex. "When welooked at HLA," Bowcock said, "we found no linkage in any of thefamilies."Psoriasis, she said, strikes about 2 percent of the population in the U.S.,3 percent in Sweden, only 0.5 percent among South American Indians.This means that about 5 million Americans suffer from the thickened,scaling skin _ particularly of scalp, elbows and knees _ for whichthere is no specific cure."Once we find the gene, of course," Bowcock observed, "therapyshould follow. "Psoriasis," she said, may be more amenable totherapeutic strategies than most diseases. "It depends on whethertreatment will be systemic or topical. Also, how the gene will be takenup by the appropriate cells, and what kinds of effects its mutation ishaving."Current treatment, she noted "is mainly targeted at some aspects of thedisease, not really knowing how it works, or why people get it." n

-- David N. Leff Science Editor

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