rs7775228

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This is a intergenic variant variant in the HLA-DQB1 gene.

Key Literature Trait Associations

Celiac Disease (HLA-DQ2.2 Haplotype Marker)

rs7775228 is a tag SNP for the HLA-DQ2.2 haplotype, one of the genetic variants in the HLA region associated with celiac disease risk. DQ2.2 alone is a much weaker celiac risk factor than DQ2.5 or DQ8, but risk increases when combined with DQ7 (creating a trans-DQ2.5-like molecule). About 3-5% of European-ancestry DQ2.2 carriers without DQ2.5 develop celiac disease. This SNP is best interpreted as part of a composite HLA-DQ haplotype panel rather than in isolation.

Kutszegi N et al. “Two tagging single-nucleotide polymorphisms to capture HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype associated with asparaginase hypersensitivity.” British Journal of Clinical Pharmacology (2021)

Allele C

OR —

p —

N 241

Candidate gene study

European

Monsuur AJ et al. “Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.” Plos One 3(5):e2270 (2008)

Allele C

OR 1.67

p 5.0e-2

Candidate gene study

Choung RS et al. “Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease.” Human Immunology (2020)

Allele C

OR —

p —

N 24,339

Preliminary work

multi-ancestry

Ting YT et al. “A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease.” Proceedings of the National Academy of Sciences of the United States of America (2020)

Allele C

OR —

p —

Candidate gene study

European

Asparaginase hypersensitivity

rs7775228-C tags the HLA-DRB1*07:01–DQA1*02:01–DQB1*02:02 haplotype, which is associated with E. coli asparaginase hypersensitivity in leukemia treatment. Combined genotyping of rs7775228 and rs28383172 identifies this risk haplotype with >95% sensitivity and specificity, enabling cost-effective pre-treatment screening to identify patients who may need alternative asparaginase formulations. The haplotype-based OR for hypersensitivity was approximately 2.0, and the two-SNP strategy provides concordance equivalent to full HLA typing at substantially lower cost.

Allele C

OR 2.00

p 2.6e-5

N 241

Candidate gene study

European

Allergic rhinitis

rs7775228-C, which cis-regulates HLA-DRB4, reached genome-wide significance for grass sensitization (p=1.6×10⁻⁹) and showed weaker association with allergic rhinitis (p=8.0×10⁻³) in a European meta-analysis of ~12,000 participants. A replication study in Han Chinese (n=1,522) confirmed association with allergic rhinitis risk (OR=1.589 for TC vs. TT genotype, p<0.001). The variant also showed first-reported association with dog allergen sensitization in a Lithuanian cohort. Collectively, evidence across multiple ancestries supports a consistent role for this HLA region variant in atopic sensitization.

Ramasamy A et al. “A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.” The Journal of Allergy and Clinical Immunology 128(5):996-1005 (2011)

Allele C

OR —

p 1.6e-9

N 12,898

Meta-analysisLarge GWAS

European

Gao Y et al. “Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese.” Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology (2020)

Allele C

OR 1.59

p 1.0e-3

N 1,522

Preliminary work

Han Chinese

Šaulienė I et al. “Genetic Loci Associated with Allergic Sensitization in Lithuanians.” Plos One (2015)

Allele C

OR —

p 8.0e-3

N 432

Candidate gene study

Lithuanian

Asthma

The rs7775228-A allele was associated with asthma risk (OR=1.17, 95% CI 1.12–1.21, p=5×10⁻¹⁵) in GWAS Catalog data from a large study, tagging the HLA-DQB1 region. Machine-learning analysis in a Chinese Zhuang cohort identified rs7775228 as one of the top six predictors for asthma (AUC=79.7%), though a direct replication study in the same Zhuang population (n=223) found no significant genotype-level difference, indicating possible population-specific effects. The A allele at this position is the common allele in most populations, so risk interpretation requires population-specific allele frequency context.

Qin ZM et al. “Importance of GWAS Risk Loci and Clinical Data in Predicting Asthma Using Machine-learning Approaches.” Combinatorial Chemistry & High Throughput Screening (2024)

Allele A

OR —

p —

N 223

Candidate gene study

Chinese (Zhuang)

Liang SQ et al. “Association of GWAS-supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population.” Journal of Clinical Laboratory Analysis (2020)

Allele A

OR —

p —

N 223

Candidate gene study

Chinese (Zhuang)

Rheumatoid arthritis

In a Japanese rheumatoid arthritis cohort (n=1,389), rs7775228 was selected by stepwise logistic regression as one of four HLA-region SNPs contributing to a haplotype associated with anti-CCP antibody positivity (haplotype OR=2.00, 95% CI 1.44–2.79, p=2.6×10⁻⁵), independently of HLA-DRB1 shared epitope status. The association reflects the broader HLA class II haplotype tagged by rs7775228 and has not been replicated at genome-wide significance in multi-ancestry RA GWAS, limiting the evidence level.

Yukinori Okada et al. “Contribution of a haplotype in the HLA region to anti–cyclic citrullinated peptide antibody positivity in rheumatoid arthritis, independently of HLA–DRB1” Arthritis & Rheumatism (2009)

Allele C

OR 2.00

p 2.6e-5

N 1,389

Preliminary work

Japanese

Knee osteoarthritis

rs7775228 reached genome-wide significance for knee osteoarthritis susceptibility in a Japanese GWAS (p=2.43×10⁻⁸, n≈4,800), implicating immunological mechanisms in osteoarthritis etiology through the HLA class II/III region. However, this association did not replicate in European populations: a large meta-analysis (n=34,660) found OR=0.94 (95% CI 0.81–1.09, p=0.42), indicating the effect may be ancestry-specific or represent population-specific LD patterns with the causal variant.

Nakajima M et al. “New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study.” Plos One 5(3):e9723 (2010)

Allele C

OR —

p 2.4e-8

N 4,800

Large GWAS

Japanese

Valdes AM et al. “Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.” Plos One (2011)

Allele C

OR 0.94

p 4.2e-1

N 34,660

Preliminary work

European

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GWAS Catalog Trait Associations (4)

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

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Research that mentions this SNP (4)

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Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: case-control study in high-level athletes

Case reportNina Briški et al.(2021)· International Orthopaedics

This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.

Traits studied:Alcohol metabolismAnxiety and panic disorderCaffeine sensitivityCholine metabolismCircadian rhythmExercise performanceFolate metabolismFood allergiesGluten sensitivityHistamine sensitivityHomocysteinemiaInflammatory markersLactose intoleranceLiver healthMicrobiota metabolismNFE2L2 pathwayObesity and weight managementOmega-3 metabolismPhase I detoxificationPhase II glutathione transferasePlant sterols metabolismRiboflavin metabolismSelenium metabolismSleep qualityUGT metabolismVitamin A metabolismVitamin B12 metabolismVitamin B6 metabolismVitamin C metabolismVitamin D metabolismVitamin K metabolismZinc metabolism

PubMed DOI Metascience Observatory

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Association analysis of two candidate polymorphisms in the Tumour Necrosis Factor-α gene with osteoarthritis in a Chinese population

AssociationN=505Bin Ji et al.(2013)· International Orthopaedics

A case-control association study examining two TNFα gene polymorphisms (rs1800629 and rs361525) and osteoarthritis susceptibility in a Han Chinese population. The rs1800629 -308A allele showed a 1.96-fold increased risk for OA (95% CI=1.33-2.89, p<0.001), while rs361525 showed no significant association.

Traits studied:Osteoarthritis

PubMed DOI Metascience Observatory

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Variability in Ethanol Biodisposition in Whites Is Modulated by Polymorphisms in the Adh1b and Adh1c Genes

ReviewCarmen Martínez et al.(2010)· Hepatology

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

Traits studied:Bone density/osteoporosisCaffeine sensitivityCardiovascular diseaseCeliac diseaseCerebrovascular diseaseCoronary heart diseaseDetoxification capacityEating behaviorGlucose homeostasisHistamine intoleranceInflammatory diseasesInsulin resistanceLactose intoleranceLeptin resistanceMetabolic syndromeNickel intoleranceObesityOsteoarthritisOverweightType 2 diabetes

PubMed DOI Metascience Observatory

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Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing

Meta-analysisN=23,143Tapio Videman et al.(2009)· Arthritis & Rheumatism

This genome-wide meta-analysis of sciatica in Finnish populations (291 cases, 3,671 controls in discovery; 776 cases, 18,489 controls in replication) identified five novel variants at two loci associated with sciatica at genome-wide significance. The strongest association was a single-base insertion rs71321981 (chr9:14344410:I) in the NFIB gene at 9p22.3 (p = 1.30×10⁻⁸, MAF = 0.08), which replicated in an independent Finnish sample (p = 0.04). Four additional variants at 15q21.2 in the MYO5A gene showed genome-wide significance (p = 1.34×10⁻⁸ to 4.78×10⁻⁸) but failed replication.

Traits studied:Degenerative lumbar spinal stenosis with radicular painLow back painLumbar disc degenerationLumbar disc herniationMusculoskeletal disordersOsteoarthritisSciatica

rs7775228

Key Literature Trait Associations

Celiac Disease (HLA-DQ2.2 Haplotype Marker)

Asparaginase hypersensitivity

Allergic rhinitis

Asthma

Rheumatoid arthritis

Knee osteoarthritis

GWAS Catalog Trait Associations (4)

Research that mentions this SNP (4)

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