Rs6010620

rs6010620 is a SNP associated with atopic dermatitis (AD). Also known as eczema, AD is one of the most common chronic inflammatory skin disorders with a prevalence estimated up to 20% in children and 3% in adults. It is a complex and highly heterogeneous disease that likely involves various genetic factors. The SNP rs6010620 locates on chromosome 20q13.33, at which there are eight genes &#8212; PRIC285, STMN3, RTEL1, TNFRSF6B, ARFRP1, ZGPAT, and LIME1 &#8212;, within a single 200-kb LD block around rs6010620. Among them, TNFRSF6B and ZGPAT might be the susceptibility candidates whose expressions correlate with the SNP as suggested by expression quantitative trait loci (eQTL) analysis.

rs6010620&#8217;s association with AD was first identified in a genome-wide association study (GWAS) published in 2011, involving 491,905 autosomal SNPs in 1,012 cases and 1,362 controls from southern China followed by two replication studies &#8212; one with an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, the other had 1,806 cases and 3,256 controls from Germany. rs6010620 showed evidence for AD association in both the combined Chinese population (minor/risk allele G; P = 3.00 &#215; 10-8; OR = 1.17) and in the German cohort (minor allele A; risk allele G; P = 2.87 &#215; 10-5; OR = 0.80).

The association was subsequently validated in a two-stage GWAS meta-analysis carried out later (P = 0.002; OR = 1.09; 95% CI 1.03&#8211;1.15). This GWAS involved 5,606 cases and 20,565 controls from 16 population-based cohorts of European descent in the discovery meta-analysis, and the ten most strongly associated new susceptibility loci were then examined in the replication meta-analysis encompassing an additional 5,419 affected individuals and 19,833 controls from 14 studies.

The group which published the first GWAS in 2011 recently validated the association as well with 4,538 cases and 13,412 controls from multiple cities in the central and northern parts of China (PGG = 1.83 &#215; 10-7; OR = 1.40; 95% CI 1.23&#8211;1.58). rs6010620&#8217;s association with subphenotypes of AD was examined in this study, and the SNP showed significant protective effect for sporadic AD (Pgenotype = 0.01; PBonferroni = 0.006; OR = 0.60; 95% CI 0.43&#8211;0.83).

Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) is an immune receptor that plays a regulatory role in suppressing cell death. It has been shown that mRNA expression of serum TNFRSF6B in AD patients are higher than those in healthy individuals and control subjects with non-atopic inflammatory diseases. ZGPAT, on the other hand, encodes the zinc finger CCCH-type with G patch domain-containing protein (ZIP) that transcriptionally represses several singling cascades including the epidermal growth factor receptor (EGFR) pathway. EGFR is overexpressed in skin lesions of AD patients and inhibition of its signaling induces dysregulated chemokine profiles that augment skin inflammation. Taken together, these results indicate that TNFRSF6B and ZGPAT are indeed plausible causal genes for AD, while further fine mapping and functional studies are still needed before an unequivocal conclusion can be made on the exact susceptibility genes at 20q13.33.

23andMe blog rs6010620 G 1.28 Glioma