rs10484554

badMag 7.5

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

Key Literature Trait Associations

Psoriasis

rs10484554 is the strongest single genetic risk factor for psoriasis, a highly accurate tag for HLA-C*06:02 (the classical psoriasis susceptibility allele). Carrying one copy increases psoriasis risk approximately 4.7-fold. HLA-C*06:02 alone accounts for as much genetic risk as all other known psoriasis loci combined. It is thought to alter how immune cells present skin proteins to T cells, triggering abnormal keratinocyte proliferation. About 32% of European psoriasis patients carry the T allele versus ~15% of controls. Environmental triggers like streptococcal infection and stress also play important roles.

Strange A et al. “A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.” Nature Genetics 42(11):985-990 (2010)
Allele T
OR 4.66
p 4.0e-214
Large GWAS
Stuart PE et al. “Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.” American Journal of Human Genetics 97(6):816-36 (2015)
Allele T
OR 3.30
p 4.0e-207
N 18,363
Large GWAS
European
Liu Y et al. “A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.” Plos Genetics 4(3):e1000041 (2008)
Allele T
OR 2.80
p 1.8e-39
N 2,112
Large GWAS
European
“The role of 39 psoriasis risk variants on age of psoriasis onset”
Allele T
OR —
p —
N 1,498
Preliminary work
European
“HLA-Cw6 and other HLA-C alleles, as well as MICB-DT, DDX58, and TYK2 genetic variants associate with optimal response to anti-IL-17A treatment”
Allele T
OR —
p —
N 62
Candidate gene study
European

Psoriatic arthritis

rs10484554-T is associated with psoriatic arthritis (PsA) as well as cutaneous psoriasis, though the HLA-C*06:02 haplotype it tags has a proportionally stronger effect on skin disease than joint disease. The Liu et al. (2008) GWAS confirmed genome-wide significant association with PsA in Northern European cohorts, and the Stuart et al. (2015) GWAS identified distinct genetic architecture between PsA and cutaneous psoriasis, with the HLA-C locus more strongly influencing the latter. Early-onset psoriatic arthritis shows particularly strong HLA-Cw6 enrichment.

Liu Y et al. “A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.” Plos Genetics 4(3):e1000041 (2008)
Allele T
OR 2.80
p 1.8e-39
N 2,112
Large GWAS
European
Stuart PE et al. “Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.” American Journal of Human Genetics 97(6):816-36 (2015)
Allele T
OR —
p 5.0e-19
N 22,363
Large GWAS
European
“The association of HLA-C and ERAP1 polymorphisms in early and late onset psoriasis and psoriatic arthritis patients of Hungary”
Allele T
OR —
p —
N 519
Preliminary work
European

HIV-1 disease progression

rs10484554-T within the MHC region on 6p21.33 has been associated with AIDS nonprogression in European HIV-infected cohorts, primarily through strong linkage disequilibrium with the HCP5 rs2395029 variant and HLA-B*57:01, which are the likely causal alleles for HIV control. The Limou et al. (2009) genome-wide study identified the HLA region as the dominant genetic determinant of HIV-1 nonprogression, with several MHC SNPs including those near HLA-C reaching genome-wide significance (p~6×10⁻⁸). The T allele at rs10484554 should be interpreted as a proxy for the broader MHC protective haplotype rather than a direct causal variant for HIV control.

Limou S et al. “Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02).” The Journal of Infectious Diseases 199(3):419-26 (2009)
Allele T
OR —
p 6.0e-8
N 1,713
Small GWAS
European
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GWAS Catalog Trait Associations (3)

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

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Research that mentions this SNP (1)

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Genome‐wide association studies and the genetic dissection of complex traits
ReviewPaola Sebastiani et al.(2009)· American Journal of Hematology

This review examines genome-wide association studies (GWAS) methodology and challenges in genetic dissection of complex traits. The authors review study design, genotyping platforms, quality control, and statistical analysis approaches for GWAS, citing key examples including associations of rs1051730 (CHRNA3) with lung cancer and nicotine dependence, rs10484554 (HLA-C) with AIDS nonprogression and psoriasis, rs2476601 (PTPN22) with Crohn's disease and type 1 diabetes, and BCL11A variants with fetal hemoglobin levels.

Traits studied:AIDS nonprogressionAge-related macular degenerationAlzheimer's diseaseBeta-thalassemiaBreast cancerChronic lymphocytic leukemiaCoronary artery diseaseCrohn's diseaseDiabetesDrug toxicityFetal hemoglobin levelsLDL cholesterolLung cancerNicotine dependenceOsteonecrosis of the jawPlatelet functionProstate cancerPsoriasisRheumatoid arthritisSickle cell anemiaTriglyceridesType 1 diabetesWarfarin maintenance dose
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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