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Cost-effective HLA typing with tagging SNPs predicts celiac disease risk haplotypes in the Finnish, Hungarian, and Italian populations |
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| Authors: | Lotta Koskinen Jihane Romanos Katri Kaukinen Kirsi Mustalahti Ilma Korponay-Szabo Donatella Barisani Maria Teresa Bardella Fabiana Ziberna Serena Vatta György Széles Zsuzsa Pocsai Kati Karell Katri Haimila Róza Ádány Tarcisio Not Alessandro Ventura Markku Mäki Jukka Partanen Cisca Wijmenga Päivi Saavalainen |
| Affiliation: | 1. Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 2. Genetics Department, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 3. Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland 4. Pediatric Research Center, University of Tampere Medical School and Tampere University Hospital, University of Tampere, Tampere, Finland 5. Coeliac Disease Center, Heim Pal Children’s Hospital, Budapest, Hungary 6. Department of Pediatrics, University of Debrecen, Debrecen, Hungary 7. Department of Experimental Medicine, Faculty of Medicine, University of Milano-Bicocca, Monza, Italy 8. Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy 9. Department of Medical Sciences, University of Milan, Milan, Italy 10. Department of Reproductive and Development Sciences, University of Trieste and IRCCS “Burlo Garofolo” Children Hospital, Trieste, Italy 11. Faculty of Public Health, Department of Epidemiology and Biostatistics, University of Debrecen, Debrecen, Hungary 12. Faculty of Public Health, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary 13. Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland 14. Department of Medical Genetics, Haartman Institute, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland |
| Abstract: | Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy. The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95% to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk effects. The method is transferable between populations and therefore suited for large-scale research studies and screening of celiac disease among high-risk individuals or at the population level. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Lotta Koskinen and Jihane Romanos are authors with equal contribution. |
| Keywords: | HLA Human leukocyte antigen Celiac disease Tagging SNP |
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