Linkage disequilibrium pattern in asthma candidate genes from 5q31-q33 in the Singapore Chinese population

Abstract

Studies have shown linkage between microsatellite markers from the chromosome 5q31-q33 region with asthma, atopy and total IgE levels in the Singapore Chinese population. However, subsequent case-control studies failed to show association between the polymorphisms in the candidate genes from this region and asthma or related phenotypes. In this study, we investigated 20 asthma candidate genes from this region for all possible informative polymorphisms within our population, linkage disequilibrium (LD) structure and tagging SNP transferability from HapMap populations. We re-sequenced these genes and identified 267 polymorphisms including 26 insertion-deletions, four microsatellite markers and 237 single nucleotide polymorphisms. The region contained 17 distinct LD blocks with the largest within the serine peptidase inhibitor kazal type 5 (SPINK5) gene spanning 23 kb. Of the 267 polymorphisms identified, 40% are represented in HapMap Han Chinese from Beijing and 29% in Han Chinese from Denver. 72% of the polymorphisms can be represented by tagged SNPs from the HapMap Beijing Han Chinese population and are highly correlated in terms of minor allele frequencies and LD structure. Our data suggest that although the HapMap Han Chinese population from Beijing is very similar to the Singapore Chinese population, this similarity is insufficient to account for up to 28% of the polymorphisms in the local population. © 2010 Blackwell Publishing Ltd/University College London.