AIM: To determine the association between the HLA-DRB1 alleles and perinuclear anti-neutrophil cytoplasmatic antibodies (p-ANCA) positive in Mexican patients with ulcerative colitis (UC).METHODS: Ninety Mexican mestizo patients (45 females) with UC, confirmed by biopsy, were studied. High resolution HLA typing was performed by PCR-SSO reverse dot blot and PCR-SSP. Molecular typing techniques were applied to define HLA-DRB1 alleles. Enzyme-linked immunosorbent assay and immunofluorescence techniques were used to detect p-ANCA.RESULTS: Forty-eight (53%) UC patients were positive for p-ANCA by ELISA and IF. We found that p-ANCA-positive UC patients had a significantly increased frequency of HLA-DR7 compared with p-ANCA-negative controls (22% vs 5.1%; pC=0.02, OR=5.2, CI 95%:1.06-37.82). Disease activity was scored as severe in 20 patients, moderate in 8, mild in 14 and no activity in the remaining 38 patients according to the Truelove and Witts criteria. Subgroup analysis showed a significantly increased frequency of the HLA-DRB1*07 allele in 15 of 20 UC patients with severe activity of UC and p-ANCA positivity [100% vs 0%; pC=0.0000001; OR=35]. No significant differences were found between p-ANCA positive patients, HLA-DR alleles and other clinical features such as extraintestinal manifestations, proctocolectomy and extension.CONCLUSION: The HLA-DRB1*07 is associated with p-ANCA positive UC Mexican patients.