Chromosome 17q12-21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first genome-wide association study correlate with expression of 2 genes, ORM1-like 3 (ORMDL3) and gasdermin B (GSDMB), making these prime candidate asthma genes, although recent studies have implicated gasdermin A (GSDMA) distal to and post-GPI attachment to proteins 3 (PGAP3) proximal to the core region as independent loci. We review 10 years of studies on the 17q12-21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early-onset asthma and mediated by PGAP3, ORMDL3, and/or GSDMA expression. We propose that the weak and inconsistent associations of 17q single nucleotide polymorphisms with asthma in African Americans is due to the high frequency of some 17q alleles, the breakdown of linkage disequilibrium on African-derived chromosomes, and possibly different early-life asthma endotypes in these children. Finally, the inconsistent association between asthma and gene expression levels in blood or lung cells from older children and adults suggests that genotype effects may mediate asthma risk or protection during critical developmental windows and/or in response to relevant exposures in early life. Thus studies of young children and ethnically diverse populations are required to fully understand the relationship between genotype and asthma phenotype and the gene regulatory architecture at this locus.

染色体17q12-21仍然是复制率最高和最重要的哮喘病位点。第一项全基因组关联研究定义的核心区域中的基因型与2个基因（ORM1样3 （ORMDL3）和gasdermin B （GSDMB））的表达相关，成为这些主要的哮喘候选基因，尽管最近的研究表明，gasdermin A  （ GSDMA）作为独立的基因座，位于GPI的远端，并在GPI后附着到最靠近核心区域的蛋白质3 （PGAP3）。我们回顾了关于17q12-21基因座的10年研究，并提出在近端和远端基因座上哮喘的基因型特异性风险不是早期发作的哮喘特异性的，而是由PGAP3，ORMDL3和/或GSDMA介导的表达。我们认为，非洲裔美国人17q单核苷酸多态性与哮喘的关联弱且不一致，是由于某些17q等位基因的频率较高，非洲衍生染色体上连锁不平衡的破坏以及这些人群中早期哮喘的内型不同孩子们。最后，哮喘与年龄较大的儿童和成年人的血液或肺细胞中基因表达水平之间的不一致关联表明，基因型效应可能会在关键的发育期和/或响应于早期生命中的相关暴露而介导哮喘风险或保护。因此，需要对幼儿和不同种族的人群进行研究，以充分了解该位点的基因型和哮喘表型与基因调控结构之间的关系。