rs2187668

badMag 7.5

This is a intron variant variant in the HLA-DQA1 gene.

Key Literature Trait Associations

Celiac Disease

rs2187668 tags the HLA-DQ2.5 haplotype (DQA1*05:01/DQB1*02:01), which is carried by approximately 90-95% of all celiac disease patients. The DQ2.5 molecule has a binding groove that preferentially accommodates deamidated gluten peptides, presenting them to gut-homing CD4+ T cells and triggering the inflammatory cascade that destroys intestinal villi. Homozygous carriers face the highest celiac risk (OR ~7.0), while heterozygous DQ2.5/DQ8 individuals also have substantial risk.

Dubois PC et al. “Multiple common variants for celiac disease influencing immune gene expression.” Nature Genetics 42(4):295-302 (2010)

Allele C

OR 7.00

p 1.0e-300

Meta-analysis

Sebastian-delaCruz M et al. “A fast, cheap, and easy protocol for celiac disease HLA haplotype typing using buccal swabs.” Methods in Cell Biology (2023)

Allele C

OR —

p —

Candidate gene study

European

Membranous glomerulonephritis

The rs2187668-A allele is strongly associated with idiopathic (primary) membranous nephropathy (iMN), an autoimmune glomerular disease causing nephrotic syndrome. A 2018 PRISMA-compliant meta-analysis of 11 studies (3,209 cases, 7,358 controls) found per-allele OR = 3.34 (95% CI 2.70–4.13) and homozygous AA vs GG OR = 12.61 (95% CI 8.02–19.81). A 2024 meta-regression of 27 studies showed the effect is substantially larger in Caucasians (OR 3.93) than East Asians (OR 2.54), and GWAS data confirm genome-wide significance (OR 4.32, p = 8×10⁻⁹³). The mechanism involves HLA-DQ2.5-mediated autoimmune targeting of the phospholipase A2 receptor (PLA2R1) on podocytes.

Bao L et al. “Association between the HLA-DQA1 rs2187668 polymorphism and risk of idiopathic membranous nephropathy: A PRISMA-compliant meta-analysis.” Medicine (2018)

Allele A

OR 3.34

p 1.0e-30

N 10,567

Meta-analysisLarge GWAS

multi-ancestry

Dhaouadi T et al. “Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression.” Biomarker Insights (2024)

Allele A

OR 3.93

p 1.0e-3

Meta-analysis

multi-ancestry

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GWAS Catalog Trait Associations (8)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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Research that mentions this SNP (2)

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Polymorphisms in the CTSH gene may influence the progression of diabetic retinopathy: a candidate-gene study in the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

AssociationN=130Steffen U. Thorsen et al.(2015)· Graefe's Archive for Clinical and Experimental Ophthalmology

This candidate gene study of 130 Danish children with type 1 diabetes examined associations between 20 diabetes-related SNPs and diabetic retinopathy progression over 16 years. The CTSH/rs3825932 variant was associated with reduced risk of progression to proliferative diabetic retinopathy (OR=0.20, p=2.4×10⁻³, p_adjust=0.048), while ERBB3/rs2292239 was associated with increased risk of two-step DR progression (OR=2.76, p=7.5×10⁻³, p_adjust=0.15). The CTSH association remained significant after multiple testing correction.

Traits studied:Diabetic retinopathyProliferative diabetic retinopathyType 1 diabetes mellitus

PubMed DOI Metascience Observatory

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Genetic variants associated with celiac disease and the risk for coronary artery disease

Meta-analysisN=86,995Henning Jansen et al.(2015)· Molecular Genetics and Genomics

This meta-analysis of 22,233 CAD cases and 64,762 controls tested 41 celiac disease-associated SNPs for association with coronary artery disease (CAD). While 58.5% of celiac disease risk alleles showed positive association with CAD (OR 1.001-1.081), this was not significantly different from the 50% expected by chance (p=0.069). Only rs653178 at the SH2B3/ATXN2 locus achieved study-wide statistical significance (OR 1.081, p=2.2×10⁻⁶), likely through pleiotropic effects. The findings provide no convincing evidence that genetic variants associated with celiac disease contribute to CAD risk.