ArticleHLA2026
Genetics of Celiac Disease in Southern Brazil: High-Resolution HLA Haplotypes and Non-HLA Polymorphisms.
Article in HLA, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Celiac disease (CeD) is an autoimmune enteropathy triggered by gluten ingestion in genetically predisposed individuals, who frequently present HLA-DQ2 or HLA-DQ8 haplotypes. To examine the genetic architecture of CeD in the admixed South Brazilian population, we sequenced the HLA alleles to high resolution and genotyped 16 non-HLA polymorphisms, previously identified through genome-wide association studies of Europeans in 171 CeD diagnosed patients and 195 controls. Controls had no CeD diagnosis, no first-degree affected relatives, and were negative for anti-TTg autoantibodies. As expected, we observed a predominance of HLA-DQA1*05:01:01~DQB1*02:01:01 (DQ2.5) and HLA-DQA1*02:01:01~DQB1*02:02:01 (DQ2.2) haplotypes among patients (51.7% and 40.2%, respectively). The ancestral 8.1 haplotype of HLA Class I and II alleles presented the highest odds of developing CeD (OR = 6.54, pcorr = 0.000065). By contrast, HLA-DQA1*01:02:01, HLA-DQB1*05:01:01, HLA-DRB1*08:02:01 and HLA-DRB1*13:01:01 were more frequent among controls (OR < 0.4, pcorr < 0.01). In contrast to results obtained in populations of predominantly European origin, HLA-DQ8 frequencies did not differ between patients and controls. Among non-HLA loci, rs6691768*G (g.61326191G > A) in NFIA was associated with protection (OR = 0.32, pcorr = 0.039) and rs653178*C (g.111569952C > T) (OR = 1.49, pcorr = 0.042) in ATXN2 was associated with susceptibility. This is the first high-resolution HLA genotyping study of CeD in Brazil, providing a comprehensive overview of genetic susceptibility in an admixed population and highlighting new potential modulatory variants beyond the classical HLA loci.
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