Clinical and Genetic Heterogeneity in Mexican Patients With Ulcerative Colitis Jesu ´ s K. Yamamoto-Furusho, Luis F. Uscanga, Gilberto Vargas-Alarco ´ n, Jorge A. Ruiz-Morales, Lorena Higuera, Teresa Cutin ˜ o, Jose ´ Manuel Rodrı ´guez-Pe ´rez, Cynthia Villarreal-Garza, and Julio Granados ABSTRACT: Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Genetic factors im- plied on its onset and severity may include genes located within the class II major histocompatibility complex (MHC) region. The aim of this study was to determine the relationship between human leukocyte antigen (HLA)- DRB1 alleles with the clinical disease patterns of UC in Mexican Mestizo patients. High-resolution HLA typing was performed by polymerase chain reaction-sequence specific oligonucleotide (PCR)-SSO reverse dot blot and PCR-single-strand polymorphism in 67 patients with UC and 99 ethnically matched healthy controls. UC patients overall showed an increased frequency of HLA-DR1 as compared with healthy controls (17.1% versus 5%, [pC = 0.003, OR = 3.9]). Patients with extensive colitis showed increased frequencies of HLA-DR1 (pC = 1  10 -10 , OR = 13.9), HLA-DRB1*0103 (pC = 1  10 -3 , OR = 21.7), HLA-DRB1*0102 (pC = 0.007, OR = undeter- mined), and HLA-DR15 (pC = 1  10 -3 , OR = 8.5) when compared with healthy controls. We also found a statistically increased frequency of HLA-DR15 in UC patients with extensive colitis compared with UC patients with only distal colitis (18.7% versus 1.8%, pC = 0.03; OR = 12.2). When patients who underwent proctocolec- tomy were compared with those who did not, an increased frequency of HLA-DRB1*0103 was observed (21.8% ver- sus 4.9%; pC = 0.03; OR = 5.4; 95% confidence inter- val, 1.39 –21.93). Also, patients with proctocolectomy showed increased frequencies of HLA-DR1 (pC = 1  10 -3 , OR = 24.2) and HLA-DRB1*0103 (pC = 1  10 -3 , OR = 50.6) when compared with healthy controls. We concluded that HLA-DR1 is associated with genetic susceptibility to UC in the Mexican Mestizo population. HLA-DR15 distinguishes a subgroup of patients with extensive colitis and the HLA-DRB1*0103 allele distin- guishes a subgroup of severe form of disease that might require surgical management. Human Immunology 64, 119 –123 (2003). © American Society for Histocompat- ibility and Immunogenetics, 2003. Published by Elsevier Science Inc. KEYWORDS: HLA; ulcerative colitis; MHC; Mexicans ABBREVIATIONS UC ulcerative colitis MHC major histocompatibility complex HLA human leukocyte antigen EIMs extraintestinal manifestations INTRODUCTION Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. However, the importance of ge- netic susceptibility has been clearly shown by epidemi- ologic information from family and twin studies [1]. The data supporting this fact include ethnic differences in disease frequency, familial aggregation, higher concor- dance in monozygotic twins, and increased occurrence of the disease in certain genetic syndromes [2, 3]. From the Department of Gastroenterology (J.K.Y.-F., L.F.U.), Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n Salvador Zubiran, Tlalpan, Mexico, Department of Physiology (G.V.A., J.M.R-P.), Instituto Nacional de Cardiologı´a Ignacio Cha ´vez, Mexico City, Mexico, and Department of Immunology and Rheumatology (J.A.R.-M., L.H., T.C., C.V.-G., J.G.), Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n Salvador Zubiran, Tlalpan, Mexico. Address reprint requests to: Dr. Julio Granados, Department of Immu- nology and Rheumatology, Instituto Nacional de Ciencias Me ´dicas y Nutri- cio ´n Salvador Zubiran, Vasco de Quiroga 15 Colonia Seccio ´n XVI, Tlalpan 14000, Mexico; Tel: (525) 5731200, ext. 2601; E-mail: kazuofurusho@ hotmail.com. Received June 25, 2002; revised September 13, 2002; accepted September 30, 2002. Human Immunology 64, 119 –123 (2003) © American Society for Histocompatibility and Immunogenetics, 2003 0198-8859/03/$–see front matter Published by Elsevier Science Inc. PII S0198-8859(02)00772-3