Dataset Information

Genetic predisposition for atopy and allergic rhinitis in the Singapore Chinese population.

ABSTRACT: The prevalence of allergic diseases is high globally, but especially in developed countries, with one in five to one in four individuals affected worldwide. The World Health Organization's "Allergic Rhinitis and its Impact on Asthma 2008 Update" guidelines stated explicitly that over 600 million patients from all countries, all ethnic groups and all ages suffer from allergic rhinitis (AR). There are clear evidences to support the concept that allergic diseases are influenced by genetic predisposition and environmental factors. The genetic basis of AR has been evaluated more intensively in the recent 10-20 years. Advances in technology and statistical methods, such as genome-wide association studies (GWAS) have enabled millions of single nucleotide polymorphisms (SNPs) to be genotyped at rapid pace and for less cost. However these studies have not yet answered the entire heritability profile of the disease. Additionally, environmental influences on these genetic variants cannot be discounted. Hence these allergic diseases must be evaluated as a complex interplay between genetic and environmental factors. This review focuses on the genetic basis of AR, with special emphasis on studies performed in Singapore. Candidate gene based studies and GWAS performed in Singapore cohorts have been discussed to suggest how these diseases could be understood better in a Singapore context which is still applicable to research in AR globally.

SUBMITTER: Wang de Y

PROVIDER: S-EPMC3206245 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Genetic predisposition for atopy and allergic rhinitis in the Singapore Chinese population.

Wang De Yun de Y

Asia Pacific allergy 20111005 3

The prevalence of allergic diseases is high globally, but especially in developed countries, with one in five to one in four individuals affected worldwide. The World Health Organization's "Allergic Rhinitis and its Impact on Asthma 2008 Update" guidelines stated explicitly that over 600 million patients from all countries, all ethnic groups and all ages suffer from allergic rhinitis (AR). There are clear evidences to support the concept that allergic diseases are influenced by genetic predispos ...[more]

PMID: 22053312

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Project description:BACKGROUND:Variation in the 10 toll-like receptor (TLR) genes has been significantly associated with allergic rhinitis (AR) in several candidate gene studies and three large genome-wide association studies. These have all investigated common variants, but no investigations for rare variants (MAF???1%) have been made in AR. The present study aims to describe the genetic variation of the promoter and coding sequences of the 10 TLR genes in 288 AR patients. METHODS:Sanger sequencing and Ion Torrent next-generation sequencing was used to identify polymorphisms in a Swedish AR population and these were subsequently compared and evaluated using 1000Genomes and Exome Aggregation Consortium (ExAC) data. RESULTS:The overall level of genetic variation was clearly different among the 10 TLR genes. The TLR10-TLR1-TLR6 locus was the most variable, while the TLR7-TLR8 locus was consistently showing a much lower level of variation. The AR patients had a total of 37 promoter polymorphisms with 14 rare (MAF???1%) and 14 AR-specific polymorphisms. These numbers were highly similar when comparing the AR and the European part of the 1000Genomes populations, with the exception of TLR10 where a significant (P?=?0.00009) accumulation of polymorphisms were identified. The coding sequences had a total of 119 polymorphisms, 68 were rare and 43 were not present in the European part of the 1000Genomes population. Comparing the numbers of rare and AR-specific SNPs in the patients with the European part of the 1000Genomes population it was seen that the numbers were quite similar both for individual genes and for the sum of all 10 genes. However, TLR1, TLR5, TLR7 and TLR9 showed a significant excess of rare variants in the AR population when compared to the non-Finnish European part of ExAC. In particular the TLR1 S324* nonsense mutation was clearly overrepresented in the AR population. CONCLUSIONS:Most TLR genes showed a similar level of variation between AR patients and public databases, but a significant excess of rare variants in AR patients were detected in TLR1, TLR5, TLR7, TLR9 and TLR10. This further emphasizes the frequently reproduced TLR10-TLR1-TLR6 locus as being involved in the pathogenesis of allergic rhinitis.

Dataset Information

Genetic predisposition for atopy and allergic rhinitis in the Singapore Chinese population.

Publications

Genetic predisposition for atopy and allergic rhinitis in the Singapore Chinese population.

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