rs12936231

This functional study examined how genetic and epigenetic factors interact to regulate gene expression at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines. The rs4795397 SNP in the ZPBP2 promoter showed strong allele-dependent effects on promoter activity in vitro (P < 0.01), with the rs4795397-A allele (HapA-associated) showing higher promoter activity and nucleosome repositioning. However, variable DNA methylation of ZPBP2 exon 1 masked the genetic effects in lymphoblastoid cell lines, while the unmethylated ORMDL3 promoter allowed detection of genetic effects.

This candidate gene association study examined genetic variants in atopic disease and proinflammatory cytokine genes for association with type 1 diabetes in 6,743-10,320 cases and 7,864-9,354 controls. The FLG R501X/rs61816761 (p=0.82), SELS -105/rs28665122 (p=0.08), and IL18 SNPs showed no association with T1D. However, four loci previously associated with asthma also showed significant association with T1D: HLA, GSDMB/ORMDL3/GSDMA (rs2305480, rs3894194, p≤1.2×10⁻⁶), and IL2RB (rs2284033, p=0.005), suggesting shared genetic susceptibility between atopic and autoimmune diseases.