A detailed Hapmap of the Sitosterolemia locus spanning 69 kb; differences between Caucasians and African-Americans

• Main Authors: Hazard Starr E, Ahn Gwang-Sook, Pandit Bhaswati, Gordon Derek, Patel Shailendra B
• Format: Article
• Language: English
• Published: BMC 2006-02-01
• Series: BMC Medical Genetics
• Online Access: http://www.biomedcentral.com/1471-2350/7/13

<p>Abstract</p> <p>Background</p> <p>Sitosterolemia is an autosomal recessive disorder that maps to the sitosterolemia locus, <it>STSL</it>, on human chromosome 2p21. Two genes, <it>ABCG5 </it>and <it>ABCG8</it>, comprise the <it>STSL </it>and mutations in either cause sitosterolemia. <it>ABCG5 </it>and <it>ABCG8 </it>are thought to have evolved by gene duplication event and are arranged in a head-to-head configuration. We report here a detailed characterization of the <it>STSL </it>in Caucasian and African-American cohorts.</p> <p>Methods</p> <p>Caucasian and African-American DNA samples were genotypes for polymorphisms at the <it>STSL </it>locus and haplotype structures determined for this locus</p> <p>Results</p> <p>In the Caucasian population, 13 variant single nucleotide polymorphisms (SNPs) were identified and resulting in 24 different haplotypes, compared to 11 SNPs in African-Americans resulting in 40 haplotypes. Three polymorphisms in <it>ABCG8 </it>were unique to the Caucasian population (E238L, INT10-50 and G575R), whereas one variant (A259V) was unique to the African-American population. Allele frequencies of SNPs varied also between these populations.</p> <p>Conclusion</p> <p>We confirmed that despite their close proximity to each other, significantly more variations are present in <it>ABCG8 </it>compared to <it>ABCG5</it>. Pairwise D' values showed wide ranges of variation, indicating some of the SNPs were in strong linkage disequilibrium (LD) and some were not. LD was more prevalent in Caucasians than in African-Americans, as would be expected. These data will be useful in analyzing the proposed role of <it>STSL </it>in processes ranging from responsiveness to cholesterol-lowering drugs to selective sterol absorption.</p>