OBJECTIVE: To screen for the Ro52 gene encoding the 52-kd Ro autoantigen for possible mutations and polymorphisms associated with primary Sjogren's syndrome (SS). METHODS: The restriction enzyme fragment-single-strand conformation polymorphism 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 results were verified by automated DNA sequencing and natural or amplification-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 prevalent among patients who were positive for anti-Ro 52-kd (20 of 38) than among healthy controls (9 of 72) (P = 0.00003); significant differences were not seen in patients who were negative for anti-Ro 52-kd. Furthermore, the frequency of the T allele in this position among groups of anti-Ro 52-kd-positive patients, anti-Ro 52-kd-negative patients, and control subjects was significantly increased in the patients who were positive for anti-Ro 52-kd compared with the controls. CONCLUSION: We present the results of a complete screening for the Ro52 gene in patients with primary SS and the results of an association study. An SNP in intron 3 was found to be strongly associated with the presence of anti-Ro 52-kd autoantibodies in primary SS. This finding is interesting in light 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 version of the Ro 52-kd protein.
OBJECTIVE: To screen for the Ro52 gene encoding the 52-kd Ro autoantigen for possible mutations and polymorphisms associated with primary Sjogren's syndrome (SS). METHODS: The restriction enzyme fragment-single-strand conformation polymorphism 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 results were verified by automated DNA sequencing and natural or amplification-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 prevalent among patients who were positive for anti-Ro 52-kd (20 of 38) than among healthy controls (9 of 72) (P = 0.00003); significant differences were not seen in patients who were negative for anti-Ro 52-kd. Furthermore, the frequency of the T allele in this position among groups of anti-Ro 52-kd-positive patients, anti-Ro 52-kd-negative patients, and control subjects was significantly increased in the patients who were positive for anti-Ro 52-kd compared with the controls. CONCLUSION: We present the results of a complete screening for the Ro52 gene in patients with primary SS and the results of an association study. An SNP in intron 3 was found to be strongly associated with the presence of anti-Ro 52-kd autoantibodies in primary SS. This finding is interesting in light 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 version of the Ro 52-kd protein.
Authors: Pamela H Williams; Beth L Cobb; Bahram Namjou; R Hal Scofield; Amr H Sawalha; John B Harley Journal: Clin Rev Allergy Immunol Date: 2007-06 Impact factor: 8.667
Authors: Alexander Espinosa; Valerie Dardalhon; Susanna Brauner; Aurelie Ambrosi; Rowan Higgs; Fransisco J Quintana; Maria Sjöstrand; Maija-Leena Eloranta; Joan Ní Gabhann; Ola Winqvist; Birgitta Sundelin; Caroline A Jefferies; Björn Rozell; Vijay K Kuchroo; Marie Wahren-Herlenius Journal: J Exp Med Date: 2009-07-27 Impact factor: 14.307