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Cysteinyl leukotriene receptor 1 gene variation and risk of asthma

¹ Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, ² Center for Population Genetics, Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, ³ Program of Population Genetics, Harvard School of Public Health, Boston, MA, USA, ⁴ Institute of Biomedicine, Anhui Medical University, Hefei, China, ⁵ Both authors contributed equally to this article.

CORRESPONDENCE: X. Xu, Center for Population Genetics, Division of Epidemiology and Biostatistics, School of Public Health M/C 923, University of Illinois at Chicago, 1603 W Taylor, Rm 978B, Chicago, IL 60612, USA. Fax: 1 3129960064. E-mail: xipingxu{at}uic.edu

Keywords: Asthma susceptibility, cysteinyl leukotriene receptor 1 gene, single nucleotide polymorphism

Received: April 17, 2008
Accepted September 11, 2008

Although it has been recognised that genetics plays an important role in the development of asthma, important causal loci remain to be identified. The aim of the present study was to examine the association of known and novel candidate genes with asthma.

Two independent samples, including 170 asthmatic cases and 347 controls in the initial sample, and 202 asthmatic cases and 332 controls in the confirmation sample, were recruited from the same region of China. Functional single nucleotide polymorphisms (SNPs; n = 129) from 105 genes were genotyped using MassARRAY technology, and 119 SNPs were used for the subsequent analysis.

In the initial sample, three SNPs, rs320995 in the cysteinyl leukotriene receptor 1 gene, rs1047266 in the tumour necrosis factor receptor superfamily, member 10b, gene and rs40401 in the interleukin-3 gene, were associated with risk of asthma. Notably, under the recessive genetic model, subjects without the thymidine allele in SNP rs320995 had a 3.1 times higher risk of asthma, which remained significant after accounting for multiple testing. This association was replicated in the confirmation sample and validated by meta-analysis. Further, sex-specific analysis was performed, but no sex difference was found.

The present study provided coherent evidence that cysteinyl leukotriene receptor 1 gene variation is associated with risk of asthma.