A GREATER VARIABILITY IN THE 3'-FLANKING REGION OF THE IL-6 GENE IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE)

The causes of the aberrant constitutive expression of cytokines in SLE have not been elucidated yet, but alterations in cytokine gene struct ure could be a contributing factor. By RFLP (Restriction Fragment Leng th Polymorphism) analysis of genomic DNA, we found a higher incidence of allelic, higher MW XbaI bands in the IL-6 genes of 9/57 SLE patient s vs 1/36 unrelated controls (p = 0.05) HLA DR/DQ typing of the polymo rphic patients revealed they were all DQ(beta)6. The study of one fami ly indicated that the XbaI polymorphic patient and her polymorphic una ffected offspring had higher than normal levels of constitutive IL-6 m RNA, The SLE-associated IL-6 XbaI restriction alleles had duplications of AT-repeat sequences, approximately 500 bp downstream of the 2(nd) polyadenylation site, in an AT-rich mini-satellite with similarities t o Matrix Associated Regions (MARs), that may be important in DNA repli cation and in gene expression, These are novel observations that sugge st that, in SLE, there is increased variability in the 3' flanking reg ion of the IL-6 gene. This variability may be related to the aberrant IL-6 expression that was reported by us and others in this disease.