Correction: Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms

Abstract

Background:The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/ DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors.Methodology: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. Conclusion:Using this method, only six SNPs were needed to predict the risk types carried by .95% of CD patients. We determined that for this tagging approach the sensitivity was .0.991, specificity .0.996 and the predictive value .0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.

Role of proneurotensin as marker of paediatric coeliac disease

“…HLA was typed with Illumina Core Exome single nucleotide polymorphism (SNP) arrays using tagged SNPs that predict the HLA-DQ alleles with high accuracy, SNP rs2187668 for DQ2.5 (A1*0501-B1*0201) and rs7454108 for DQ8 (A1*0301-B1*0302) [25]. HLA-DQ haplotypes were divided into five genotype groups: (1) DQ2.5/2.5 (homozygous DQ2.5), (2) DQ2.5/x (heterozygous DQ2.5/ x, where x is any other haplotype than DQ8 or DQ2.5), (3) DQ2/8 (heterozygous patients carrying DQ2.5/DQ8), (4) DQ8/x (homozygous DQ8/8 or heterozygous DQ8/x, where x is any other haplotype than DQ8 or DQ2.5) and (5) other (patients carrying neither DQ2.5 nor DQ8).…”