TY - JOUR
T1 - Cost-effective HLA typing with tagging SNPs predicts celiac disease risk haplotypes in the Finnish, Hungarian, and Italian populations
AU - Koskinen, Lotta
AU - Romanos, Jihane
AU - Kaukinen, Katri
AU - Mustalahti, Kirsi
AU - Korponay-Szabo, Ilma
AU - Barisani, Donatella
AU - Bardella, Maria Teresa
AU - Ziberna, Fabiana
AU - Vatta, Serena
AU - Szeles, Gyoergy
AU - Pocsai, Zsuzsa
AU - Karell, Kati
AU - Haimila, Katri
AU - Adany, Roza
AU - Not, Tarcisio
AU - Ventura, Alessandro
AU - Maeki, Markku
AU - Partanen, Jukka
AU - Wijmenga, Cisca
AU - Saavalainen, Paeivi
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - HLA
KW - Human leukocyte antigen
KW - Celiac disease
KW - Tagging SNP
KW - SINGLE NUCLEOTIDE POLYMORPHISMS
KW - EUROPEAN GENETICS CLUSTER
KW - ASSOCIATION
KW - DQ
KW - HETERODIMER
KW - FAMILIES
KW - SUSCEPTIBILITY
KW - DIAGNOSIS
KW - ALLELES
KW - PROGRAM
U2 - 10.1007/s00251-009-0361-3
DO - 10.1007/s00251-009-0361-3
M3 - Article
SN - 0093-7711
VL - 61
SP - 247
EP - 256
JO - Immunogenetics
JF - Immunogenetics
IS - 4
ER -