A common functional promoter variant links CNR1 gene expression to HDL cholesterol level
A common functional promoter variant links CNR1 gene expression to HDL cholesterol level
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DOI：
10.1038/ncomms2973
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发表时间：
2013-06-01
影响因子：
16.6
通讯作者：
Wilke, R. A.
中科院分区：
文献类型：
--
作者：
Feng, Q.;Vickers, K. C.;Wilke, R. A.
Type 1 cannabinoid receptor blockers increase high-density lipoprotein cholesterol levels. Although genetic variation in the type 1 cannabinoid receptor-encoded by the CNR1 gene-is known to influence high-density lipoprotein cholesterol level as well, human studies conducted to date have been limited to genetic markers such as haplotype-tagging single nucleotide polymorphisms. Here we identify rs806371 in the CNR1 promoter as the causal variant. We re-sequence the CNR1 gene and genotype all variants in a DNA biobank linked to comprehensive electronic medical records. By testing each variant for association with high-density lipoprotein cholesterol level in a clinical practice-based setting, we localize a putative functional allele to a 100-bp window in the 5'-flanking region. Assessment of variants in this window for functional impact on electrophoretic mobility shift assay identifies rs806371 as a novel regulatory binding element. Reporter gene assays confirm that rs806371 reduces gene expression, thereby linking CNR1 gene variation to high-density lipoprotein cholesterol level in humans.
