title: Cost-effective HLA typing with tagging SNPs predicts celiac disease risk haplotypes in the Finnish, Hungarian, and Italian populations.
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.
authors.affiliation: Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Koskinen
authors.forename: Jihane
authors.initials: J
authors.lastname: Romanos
authors.forename: Katri
authors.initials: K
authors.lastname: Kaukinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Mustalahti
authors.forename: Ilma
authors.initials: I
authors.lastname: Korponay-Szabo
authors.forename: Donatella
authors.initials: D
authors.lastname: Barisani
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bardella
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ziberna
authors.forename: Serena
authors.initials: S
authors.lastname: Vatta
authors.forename: György
authors.initials: G
authors.lastname: Széles
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Pocsai
authors.forename: Kati
authors.initials: K
authors.lastname: Karell
authors.forename: Katri
authors.initials: K
authors.lastname: Haimila
authors.forename: Róza
authors.initials: R
authors.lastname: Adány
authors.forename: Tarcisio
authors.initials: T
authors.lastname: Not
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ventura
authors.forename: Markku
authors.initials: M
authors.lastname: Mäki
authors.forename: Jukka
authors.initials: J
authors.lastname: Partanen
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Päivi
authors.initials: P
authors.lastname: Saavalainen
mesh_terms: D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology; D005820:Genetic Testing / Q000191:economics / Q000379:methods*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: D006680:HLA Antigens