Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
PLoS One. 2011;6(5):e19719. doi: 10.1371/journal.pone.0019719. Epub 2011 May 20.
Allergic rhinitis (AR) is an atopic disease which affects about 600 million people worldwide and results from a complex interplay between genetic and environmental factors. However genetic association studies on known candidate genes yielded variable results. The aim of this study is to identify the genetic variants that influence predisposition towards allergic rhinitis in an ethnic Chinese population in Singapore using a genome-wide association study (GWAS) approach. A total of 4461 ethnic Chinese volunteers were recruited in Singapore and classified according to their allergic disease status. The GWAS included a discovery stage comparing 515 atopic cases (including 456 AR cases) and 486 non-allergic non-rhinitis (NANR) controls. The top SNPs were then validated in a replication cohort consisting of a separate 2323 atopic cases (including 676 AR cases) and 511 NANR controls. Two SNPs showed consistent association in both discovery and replication phases; MRPL4 SNP rs8111930 on 19q13.2 (OR = 0.69, P(combined) = 4.46×10(-05)) and BCAP SNP rs505010 on chromosome 10q24.1 (OR = 0.64, P(combined) = 1.10×10(-04)). In addition, we also replicated multiple associations within known candidates regions such as HLA-DQ and NPSR1 locus in the discovery phase. Our study suggests that MRPL4 and BCAP, key components of the HIF-1α and PI3K/Akt signaling pathways respectively, are two novel candidate genes for atopy and allergic rhinitis. Further study on these molecules and their signaling pathways would help in understanding of the pathogenesis of allergic rhinitis and identification of targets for new therapeutic intervention.
变应性鼻炎（AR）是一种影响全球约 6 亿人的特应性疾病，是遗传和环境因素复杂相互作用的结果。然而，针对已知候选基因的遗传关联研究得出的结果各不相同。本研究旨在采用全基因组关联研究（GWAS）方法，鉴定影响新加坡华人种族群体变应性鼻炎易感性的遗传变异。共招募了 4461 名新加坡华人志愿者，并根据其过敏性疾病状况进行分类。GWAS 包括一个比较 515 例特应性病例（包括 456 例 AR 病例）和 486 例非过敏性非鼻炎（NANR）对照的发现阶段。然后，在一个由 2323 例特应性病例（包括 676 例 AR 病例）和 511 例 NANR 对照组成的复制队列中验证了顶级 SNP。在发现和复制阶段，有两个 SNP 显示出一致的关联；19q13.2 上的 MRPL4 SNP rs8111930（OR=0.69，P(联合)=4.46×10(-05))和 10q24.1 上的 BCAP SNP rs505010（OR=0.64，P(联合)=1.10×10(-04)）。此外，我们还在发现阶段复制了 HLA-DQ 和 NPSR1 基因座等已知候选区域的多个关联。我们的研究表明，MRPL4 和 BCAP 分别是 HIF-1α 和 PI3K/Akt 信号通路的关键组成部分，是特应性和变应性鼻炎的两个新候选基因。对这些分子及其信号通路的进一步研究将有助于理解变应性鼻炎的发病机制，并确定新治疗干预的靶点。
