HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in north-western Mexico

Abstract

BackgroundType 1 diabetes (T1D) and celiac disease (CD) are the two most common autoimmune childhood diseases that share their HLA-DQ2 and DQ8 genetic origin. There has been a current increase in both diseases worldwide. In children from the low-population State of Sonora (15 inhabitants/km2) in northwestern Mexico, there is no information on their genetic risk or the distribution of the related alleles in the general population. AimsTo compare the HLA-DQ allele frequency in a representative sample of newborns from Sonora with that of T1D and CD patients to determine the risk gradient and identify the presence of celiac autoimmunity in the T1D group. MethodsThe study included 397 Sonoran newborns, 44 cases of T1D, and 25 CD cases. The CD and T1D cases were clinically diagnosed by specialists at the Hospital Infantil del Estado de Sonora and the autoantibodies were determined by ELISA. Whole blood was collected, gDNA was extracted, and HLA-DQ2 and DQ8 were typed by PCR-SSP. The risk gradient was calculated by comparing the allele frequencies of the cases with those of the newborns. ResultsThe Sonoran HLA-DQ risk heterodimer proportion was 16.1% for HLA-DQ2 and 13.6% for HLA-DQ8 with an HLA-DQ2: HLA-DQ8 ratio of 1.2:1. The DQ8/DQ2 genotype represented a 1:14 risk for T1D, whereas the DQ8/DQB1*0201 combination resulted in a 1:6 risk for CD. The prevalence of CD autoimmunity in T1D children was 7%. ConclusionThe Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases and T1D and CD frequently appear together.