Combination Testing Using a Single MSH5 Variant alongside HLA Haplotypes Improves the Sensitivity of Predicting Coeliac Disease Risk in the Polish Population

• DOI: 10.1371/journal.pone.0139197
• Publication Date: 2015-09-25T18:25:49Z
• Authors: Agnieszka Paziewska; Bozena Cukrowska; Michalina Dabrowska; Krzysztof Goryca; Magdalena Piatkowska; Anna Kluska; Michal Mikula; Jakub Karczmarski; Beata Oralewska; Anna Rybak; Jerzy Socha; Aneta Balabas; Natalia Zeber-Lub...; Filip Ambrozkiewicz; Ewa Konopka; Ilona Trojanowska; Malgorzata Zagroba; Malgorzata Szperl; Jerzy Ostrowski
• Keywords: Genome-wide Association Study; SNP; Genetic Association

Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification potential coeliac disease (CD) patients. We intended identify new genetic associated with CD in Polish population that would risk prediction when used haplotype analysis. DNA samples 336 and 264 unrelated healthy controls were create pools for a genome wide association study (GWAS). GWAS findings validated individual tag single nucleotide polymorphism (SNP) typing 473 patients 714 controls. Association analysis using four HLA-tagging SNPs showed that, as found other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, HLA-DQ2.5/DQ8) at higher frequencies than control individuals population. Both CD-associated discovered by susceptibility region, confirming previously-determined major histocompatibility (MHC) region pathogenesis. The two most significant from rs9272346 (HLA-dependent; localized within 1 Kb DQA1) rs3130484 (HLA-independent; mapped MSH5). Specificity achieved 92.9%, but sensitivity only 45.5%. However, combination MSH5 SNP used, specificity decreased 80%, increased 74%. This confirmed improvement could be including testing.