Polymorphisms of the Ro52 gene associated with anti-Ro 52-kd autoantibodies in patients with primary Sjogren's syndrome

Objective. To screen for the Ro52 gene encoding the 52-kd Ro autoantigen fo r possible mutations and polymorphisms associated with primary Sjogren's sy ndrome (SS). Methods. The restriction enzyme fragment-single-strand conformation polymor phism method was used to search for mutations and polymorphisms in the Ro52 gene in 97 patients with primary SS and 72 healthy control subjects. The r esults were verified by automated DNA sequencing and natural or amplificati on-created restriction site tests. Results. A single-nucleotide polymorphism (SNP) was discovered in intron 3 (137 bp upstream of exon 4). The C/T genotype was significantly more preval ent among patients who were positive for anti-Ro 52-kd (20 of 38) than amon g healthy controls (9 of 72) (P = 0.00003); significant differences were no t seen in patients who were negative for anti-Ro 52-kd. Furthermore, the fr equency of the T allele in this position among groups of anti-Ro 52-kd-posi tive patients, anti-Ro 52-kd-negative patients, and control subjects was si gnificantly increased in the patients who were positive for anti-Ro 52-kd c ompared with the controls. Conclusion. We present the results of a complete screening for the Ro52 gen e in patients with primary SS and the results of an association study. An S NP in intron 3 was found to be strongly associated with the presence of ant i-Ro 52-kd autoantibodies in primary SS. This finding is interesting in lig ht of the fact that an alternative messenger RNA is made by deleting exon 4 , which encodes a putative leucine zipper domain, to generate a shorter ver sion of the Ro 52-kd protein.