X-CHROMOSOME INACTIVATION IN MONOZYGOTIC TWINS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

The hypothesis that a low concordance rate in monozygotic (MZ) twins w ith systemic lupus erythematosus (SLE) may be accounted for by differe nces in X-chromosome inactivation was examined. Five MZ twin pairs, fo ur discordant and one concordant, were recruited, zygosity confirmed b y DNA fingerprinting, and their pattern of X-chromosome inactivation i n DNA samples prepared from peripheral blood and buccal cells were exa mined. X-chromosome inactivation was assessed by the methylation statu s of the CpG region near trinucleotide repeats in exon 1 of the androg en receptor gene on X-chromosome after digestion with the methylation- sensitive enzyme HpaII or HhaI and PCR amplification. X-chromosome ina ctivation patterns were found to be the same between affected and non- affected twins in all four discordant twin pairs, with random patterns in two pairs and skewed patterns in the others. The concordant twins demonstrated the same random patterns. X-chromosome inactivation was a lso examined from buccal smear DNA and shown to have the same pattern as that noted from peripheral blood DNA in one informative twin pair. Differences in X-chromosome inactivation patterns were not observed in these five MZ twin pairs. The results could not support the hypothesi s that differences in X-chromosome inactivation is the mechanism accou nting for the low concordance rate noted in MZ twins with SLE.