rs11204971 — FLG FLG locus regulatory variant

Tag SNP in the filaggrin (FLG) locus associated with elevated atopic dermatitis risk — strongly enriched in East Asian populations where the G allele reaches 57% frequency

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FLG Locus — Skin Barrier Regulation and the Atopic March

Filaggrin is the key structural protein of the outermost skin layer. Encoded by the FLG gene at chromosome 1q21.3, it aggregates keratin filaments into the waterproof matrix of the stratum corneum11 aggregates keratin filaments into the waterproof matrix of the stratum corneum
Profilaggrin is cleaved into 10–12 filaggrin monomers during terminal epidermal differentiation; the monomers compact keratin and their breakdown products form NMF — the mixture of amino acids, urocanic acid, and urea that keeps skin hydrated and acidic. When filaggrin levels are reduced — through coding mutations that eliminate protein entirely, or through regulatory variants that lower expression — transepidermal water loss rises, skin pH increases, and gaps form between surface skin cells that allow environmental allergens to penetrate and trigger immune sensitization.

rs11204971 is a tag SNP in the FLG locus identified in genome-wide association studies of atopic dermatitis in Chinese Han populations. The G allele shows a striking population distribution: approximately 57% frequency in East Asians compared to 14% in Europeans and 4% in Africans, reflecting the distinct spectrum of FLG variation across ancestry groups.

The Evidence

The FLG 1q21.3 locus was confirmed in a large Chinese Han GWAS22 large Chinese Han GWAS
Sun et al. 2011: 1,012 AD cases and 1,362 controls in discovery, 3,624 cases and 12,197 controls in replication, plus 1,806 German cases; tag SNP rs3126085 showed OR=0.82 (P=5.90×10⁻¹²) for the protective allele. rs11204971 was used alongside rs3126085 as a secondary tag SNP for this locus in follow-up Chinese Han studies33 follow-up Chinese Han studies
Tang et al. 2012: examined rs11204971 and rs3126085 alongside three other AD susceptibility SNPs, finding FLG association with AD but not asthma in 463 asthma cases and 985 controls — suggesting distinct genetic architectures for the two atopic conditions.

The broader FLG literature — built primarily on coding loss-of-function mutations — shows robust effects. A meta-analysis of 24 studies44 meta-analysis of 24 studies
Van den Oord & Sheikh 2009: 5,791 eczema cases, 26,454 controls; asthma analysis in 17 studies found FLG haploinsufficiency associated with eczema at OR 3.12 (95% CI 2.57–3.79) and the combined eczema-plus-asthma phenotype at OR 3.29. Importantly, the asthma association was only present in the context of existing eczema — FLG variants do not independently predispose to asthma absent skin barrier disruption — supporting a percutaneous sensitization model where allergens breach the defective skin barrier, trigger IgE-mediated sensitization, and drive the downstream atopic march.

Interactions

rs11204971 tags the same FLG locus haplotype as rs3126085.

rs11204971 shows no independent association with asthma in the absence of atopic dermatitis, which is consistent with the percutaneous sensitization model: FLG-driven systemic Th2 skewing requires active barrier disruption and allergen penetration through eczematous skin.

Genotype Interpretations

What each possible genotype means for this variant.

AA Normal expression Normal

Common FLG locus genotype — normal filaggrin expression expected

You carry two copies of the reference A allele at this FLG locus position, which is associated with normal filaggrin expression. This genotype is found in approximately 72% of the global population and is the dominant genotype in people of African ancestry (approximately 92% AA). About 73% of Europeans and 18% of East Asians carry this genotype. No elevated risk for atopic dermatitis or skin barrier disruption is associated with this variant based on current evidence.

AG One risk haplotype Intermediate

One copy of the FLG risk haplotype — moderately elevated atopic dermatitis susceptibility

The clinical impact of heterozygosity for this regulatory variant is subtler than for coding null mutations: many AG carriers will have no eczema symptoms, and the variant contributes modest odds of atopic dermatitis rather than the OR 3.1 seen for coding null allele heterozygotes. In East Asian populations where the G allele is common, AD risk from this locus is a population-level contributor rather than a marker of extreme individual risk.

GG Two risk haplotypes High Risk

Two copies of the FLG risk haplotype — elevated atopic dermatitis risk, particularly in East Asian individuals

In East Asian populations, GG is the most common single genotype at this locus (more common than AA at ~32% vs 18%), so a large proportion of East Asian individuals with atopic dermatitis will carry this genotype. The risk attributable to GG is additive over AG in an additive inheritance model. If you have personal or family history of atopic dermatitis, asthma, or food allergy — especially if you are of East Asian or South Asian ancestry — GG at this locus is an expected finding that explains some of that susceptibility.