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Genetics

Variants in ASGR1 linked to reduced CAD risk

Nature Reviews Cardiology volume 13, page 442 (2016)Cite this article

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Given that non-HDL cholesterol encompasses all cholesterol-containing proatherogenic lipoproteins, it is believed to be a better predictor of coronary artery disease (CAD) risk than LDL cholesterol alone. To identify new genetic variants that affect the levels of non-HDL cholesterol, Nioi and colleagues sequenced the genome of 2,636 individuals from Iceland, and found a noncoding 12-base-pair deletion in intron 4 of ASGR1, a major subunit of the asialoglycoprotein receptor that can mediate the endocytosis and degradation of numerous desialylated glycoproteins. Heterozygous carriers of this ASGR1 variant had a lower level of non-HDL cholesterol (P = 1.0×10−16), in addition to a 34% lower risk of CAD (95% CI 21–45, P = 4.0×10−6). In a larger set of sequenced samples from the Icelandic individuals, another loss-of-function ASGR1 variant associated with lower non-HDL cholesterol levels was identified. According to the investigators, “these variants disrupt ASGR1 function and represent a link between the sialylation pathway and atherosclerotic diseases.

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References

  1. Nioi, P. et al. Variant ASGR1 associated with a reduced risk of coronary artery disease. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1508419 (2016)

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Authors
  1. Karina Huynh
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Huynh, K. Variants in ASGR1 linked to reduced CAD risk. Nat Rev Cardiol 13, 442 (2016). https://doi.org/10.1038/nrcardio.2016.90

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