Investigation of HLA-DPA1 genotypes as predictors of inflammatory bowel disease in the German, South African, and South Korean populations

Annette Lantermann, Jochen Hampe, Won H. Kim, Trevor A. Winter, Mark Kidd, Marion Nagy, Ulrich R. Fölsch, Stefan Schreiber

A1 Department of General Internal Medicine, Christian Albrechts University, Schittenhelmstrasse 12, 24105 Kiel, Germany
A2 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
A3 Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
A4 Institute for Forensic Medicine, Charité University Hospital, Berlin, Germany


Abstract. Background and aims: Inflammatory bowel disease (IBD) is a polygenic disorder, as demonstrated by epidemiological evidence, genetic linkage, and the identification of the first susceptibility gene, NOD2. Genetic linkage analysis has identified and replicated several genomic regions as locations for susceptibility genes, including chromosome 6p (termed IBD3). The HLA-DP genes play an important role in antigen presentation and are located within the chromosome 6p linkage region. Patients and methods: We investigated HLA-DPA1 as a positional and functional candidate gene for IBD using 249 German multiplex IBD families, 174 unrelated German controls, 48 monoplex families from a mixed South African population, 87 IBD patients, and 71 controls from a South Korean sample. Polymorphisms in exon 2 at amino acid positions 31, 37-38 and 50 were genotyped using direct sequencing. Analyses were performed using L2 statistics, multipoint transmission disequilibrium test and nonparametric linkage analysis. Results: A marginally significant association for Crohn's disease was detected in the German family cohort for DPA1*02021. This finding was not replicated in ulcerative colitis or any of the other populations. Conclusion: HLA-DPA1 is not a major determinant of IBD risk in any of the three populations. The transmission distortion observed in the German cohort may indicate an extended haplotype, suggesting another disease relevant gene in the vicinity of HLA-DPA.