A Common Copy Number Variation on Chromosome 6 Association With the Gene Expression Level of Endothelin 1 in Transformed B Lymphocytes From Three Racial Groups

Background-Previous studies indicate that the endothelin system is involved in hypertension, heart failure, atherosclerosis, chronic kidney disease, and diabetes. To explore the potential genetic effects of copy number variations (CNVs) on the endothelin system, which underlie these diseases, we studied the association of genome-wide CNVs with gene expression levels of 7 genes involved in the endothelin system using independent HapMap subjects including 90 Asians (45 Han Chinese and 45 Japanese), 60 whites, and 60 blacks. Methods and Results-For each subject, the genome-wide variations were measured using the Affymetrix 6.0 chip that includes measurements of 906 000 single-nucleotide polymorphisms and 946 000 CNV probes. The gene expression profiles of the transformed B lymphocytes were measured for the same subjects. Among the 210 subjects, we identified 1529 CNV regions on 22 autosomes. By testing the association between CNVs and the gene expression levels in each racial group using linear regression, we identified 4 statistically significant CNV associations in all 3 groups (alpha = 0.05). The strongest association was between a 66 kbp CNV region located on chromosome 6 and endothelin-1 (EDN1) expression. The effects of the CNV-EDN1 association in the 3 racial groups were in the same direction and explained 7% to 14% of the variation in EDN1 expression. Conclusions-Although the biological function of the chromosome 6 CNV is unclear, the significant and consistent association found in 3 racial groups suggests that CNVs may contribute to variation in underlying risks of common disease through their effects on key molecular signaling pathways. (Circ Cardiovasc Genet. 2009;2:483-488.)