1. ¹Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY, USA
2. ²Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN, USA
3. ³Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA
4. ⁴The Center for Human Genetics Research and Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
5. ⁵Hallym Institution for Genome Application, Hallym University Sacred Heart Hospital, Anyang, South Korea
6. ⁶Hanyang University College of Medicine, Hospital for Rheumatic Diseases, Seoul, South Korea

Correspondence: Professor PK Gregersen, Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA. E-mail: peterg@nshs.edu

Received 6 April 2006; Revised 12 June 2006; Accepted 12 June 2006; Published online 20 July 2006.

Abstract

The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1^*09 and DRB1^*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility.