Polymorphisms and haplotypes of the chromosome locus 17q12-17q21.1 contribute to adult asthma susceptibility in Slovenian patients

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• 作者：Mateja Žavbi ; Peter Koro&scaron ; ec ; Matjaž Fležar ; Sabina &Scaron ; krgat Kristan ; Mateja Marc Malovrh ; Matija Rijavec ; ^{matija.rijavec@klinika-golnik.si" class="auth_mail" title="E-mail the corresponding author}
• 关键词：GWAS ; genome-wide association study ; SNP ; single nucleotide polymorphism ; CSF3 ; colony stimulating factor 3 ; ORMDL3 ; ORM1-like 3 (S. cerevisiae) ; MED24 ; mediator complex subunit 24 ; GSDMA ; gasdermin A ; GSDMB ; gasdermin B ; PSMD3 ; proteasome non-ATPase regulatory subunit 3 ; ZBPB2 ; zona pellucida binding protein 2 ; LD ; linkage disequilibrium ; FEV1% ; percentage of predicted forced expiratory volume in 1  ; s ; VC% ; percentage of lung vital capacity ; PCR ; polymerase chain reaction ; ORs ; odds ratios
• 刊名：Human Immunology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：77
• 期：6
• 页码：527-534
• 全文大小：879 K

文摘

One of the major asthma susceptibility loci is 17q12-17q21.1, but the relationship between this locus and adult asthma is unclear. Association analysis of 13 single nucleotide polymorphisms (SNPs) and haplotypes from 17q12-17q21.1 was performed in 418 adult patients with asthma and 288 controls from Slovenia. Single SNP analysis revealed only marginal associations with adult asthma for SNPs located in GSDMA, GSDMB, ORMDL3 and ZPBP2 genes, and rs7219080 was the most highly associated. Analyses of asthma phenotypes found no association with atopy or lung function, but rs2305480 and rs8066582 were associated with childhood asthma and rs9916279 was associated with asthma in smokers. Notably, haplotypes consisting of rs9916279, rs8066582, rs1042658, and rs2302777 harbouring PSMD3, CSF3 and MED24 genes were highly associated with asthma. The four most common haplotypes, TCCG, TTTA, CCCA and TTCA, were more frequent in patients with asthma, whereas TTCG, TCCA, TCTA and TTTG were more frequent in controls. Only 3% of asthma patients belonged to haplotypes TTCG, TCCA, TCTA and TTTG compared with nearly one-third (31%) of controls. Associations confirmed that the 17q12-17q21.1 locus harbours a genetic determinant for asthma risk in adults and suggest that in addition to the previously known ORMDL3-GSDM locus, CSF3-PSMD3-MED24 also plays a role in asthma pathogenesis.