title: Deficient repair of O6-methylguanine in lymphocytes from rheumatoid arthritis families may be an acquired defect.
abstract: Deficient repair of the premutagenic DNA lesion O6-methylguanine (O6-MeGua) has been reported in lymphocytes from patients with autoimmune diseases. This was confirmed in the present study of probands with rheumatoid arthritis (RA) and their families. We also noted a significant deficiency in 9/19 spouses (P less than 0.05) and a statistically non-significant deficiency of repair of O6-MeGua in 14/42 first and second degree relatives in comparison with healthy and non-autoimmune disease controls, respectively. A significant correlation of the repair status of O6-MeGua in DNA between individual probands with RA and respective spouses (P less than 0.01) and probands and respective family members (P less than 0.001) supported the idea that an environmental, transmissible agent could influence the expression of the protein, O6-methylguanine-DNA-transferase (O6-MT), involved in the repair of O6-MeGua. The present results, however, cannot entirely exclude an additional hereditary influence.
authors.affiliation: Department of Immunology, Middlesex Hospital Medical School, London, UK.
authors.forename: C B
authors.initials: CB
authors.lastname: Colaço
authors.forename: G
authors.initials: G
authors.lastname: Harris
authors.forename: P D
authors.initials: PD
authors.lastname: Lawley
authors.forename: P M
authors.initials: PM
authors.lastname: Lydyard
authors.forename: I M
authors.initials: IM
authors.lastname: Roitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics; D001327:Autoimmune Diseases / Q000097:blood* / Q000235:genetics; D004260:DNA Repair; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D006147:Guanine; C008449:O-(6)-methylguanine