rs4349859

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

Key Literature Trait Associations

Ankylosing Spondylitis

rs4349859 is a tag SNP for HLA-B27, one of the strongest genetic risk factors known in all of human genetics. About 80-90% of people with ankylosing spondylitis (a chronic inflammatory arthritis of the spine) carry HLA-B27, versus ~8% of the general European population. However, only about 1-5% of HLA-B27-positive individuals develop the disease. Carrying the A allele indicates ~98% probability of carrying HLA-B27 in Europeans (98% sensitivity, 99% specificity). This tag SNP is less accurate in African or East Asian populations where different HLA-B27 subtypes predominate.

Evans DM et al. “Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.” Nature Genetics 43(8):761-767 (2011)

Allele A

OR 48.90

p 1.0e-200

Large GWAS

Fernández-Torres J et al. “MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis.” Immunologic Research (2024)

Allele A

OR 9.22

p 1.0e-3

Candidate gene study

Mexican

Joshi R. et al. “Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?” Arthritis Care & Research (2012)

Allele A

OR 4.44

p 1.0e-4

N 502

Preliminary work

multi-ancestry

Martínez-Nava GA et al. “A proposed HLA-B*27 screening method for ankylosing spondylitis detection based on tag-single nucleotide polymorphisms: a preliminary study.” Molecular Biology Reports (2021)

Allele A

OR —

p —

Candidate gene study

Mexican

Thionamide-induced agranulocytosis

The A allele of rs4349859, located in the MICA gene region, was one of five MICA SNPs significantly associated with thionamide-induced agranulocytosis (TIA) after Bonferroni correction in a Chinese cohort (p=1.43×10⁻⁷). Haplotype analysis combining rs4349859 with HLA-B*27:05 data yielded an OR of 14.85 (95% CI 3.63–60.77, p=9.76×10⁻⁷) for TIA. The study included 37 TIA cases and 254 Graves' disease controls, and these findings require confirmation in larger, independent studies.

Ma P et al. “Association of MICA gene polymorphisms with thionamide-induced agranulocytosis.” Journal of Endocrinological Investigation (2021)

Allele A

OR 14.85

p 1.4e-7

N 291

Preliminary work

Chinese

Gout

The A allele of rs4349859 has been associated with gout susceptibility in a Mexican candidate-gene study, with an extraordinarily large reported OR of 146 (95% CI 44.8–480.2), likely reflecting small sample size (n=176) and strong HLA-B*27 LD in this population. A companion study confirmed significant risk associations (p<0.01) for gout, with gene-gene interactions between HLA-B and NLRP3 polymorphisms also implicated. The A allele carrier genotype (GA) was also linked to significantly elevated serum urate levels compared to non-carriers. These findings require replication in larger, independent cohorts before clinical conclusions can be drawn.

Fernández-Torres J et al. “Relationship between rs4349859 and rs116488202 polymorphisms close to MHC-I region and serum urate levels in patients with gout.” Molecular Biology Reports (2023)

Allele A

OR 146.00

p 1.0e-2

N 176

Candidate gene study

Mexican

Fernández-Torres J et al. “The interplay between HLA-B and NLRP3 polymorphisms may be associated with the genetic susceptibility of gout.” Molecular Biology Reports (2022)

Allele A

OR —

p 1.0e-2

N 176

Candidate gene study

Mexican

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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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Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?

AssociationN=502Joshi R. et al.(2012)· Arthritis Care & Research

This association study compared genetic susceptibility loci frequencies between 312 familial and 190 sporadic ankylosing spondylitis (AS) cases. HLA-B27 was significantly more prevalent in familial cases (OR: 5.41, p=8.4×10⁻⁸), while non-MHC susceptibility variants in IL23R, IL1R2, ANTXR2, ERAP1, and intergenic regions on chromosomes 2p15 and 21q22 showed no significant differences between familial and sporadic cases.

rs4349859

Key Literature Trait Associations

Ankylosing Spondylitis

Thionamide-induced agranulocytosis

Gout

GWAS Catalog Trait Associations (3)

Research that mentions this SNP (1)

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