Common Low-Density Lipoprotein Receptor p.G116S Variant Has a Large Effect on Plasma Low-Density Lipoprotein Cholesterol in Circumpolar Inuit Populations

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dc.contributor.authorDubé, Joseph B.
dc.contributor.authorWang, Jian
dc.contributor.authorCao, Henian
dc.contributor.authorMcIntyre, Adam D.
dc.contributor.authorJohansen, Christopher T.
dc.contributor.authorHopkins, Scarlett E.
dc.contributor.authorStringer, Randa
dc.contributor.authorHosseinzadeh, Siyavash
dc.contributor.authorKennedy, Brooke A.
dc.contributor.authorBan, Matthew R.
dc.contributor.authorYoung, T. Kue
dc.contributor.authorConnelly, Philip W.
dc.contributor.authorDewailly, Eric
dc.contributor.authorBjerregaard, Peter
dc.contributor.authorBoyer, Bert B.
dc.contributor.authorHegele, Robert A.
dc.coverage.spatialAlaska
dc.coverage.spatialCanada
dc.coverage.spatialGreenland
dc.date.accessioned2025-05-01T12:28:10Z
dc.date.available2025-05-01T12:28:10Z
dc.date.issued2014-11-20T00:00:00+00:00
dc.description"Background: Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p.G116S and p.R730W. Methods and Results: Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6×10−49), which was >3× larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34–3.90; P=1.7×10−17), but did not have classical familial hypercholesterolemia. In vitro, p.G116S showed 60% reduced ligand-binding activity compared with wild-type receptor. In contrast, p.R730W was associated with neither LDL cholesterol level nor altered in vitro activity." (as cited in abstract)
dc.identifier.doihttps://doi.org/10.7939/r3-jez3-fh39
dc.language.isoen
dc.relation<https://v2.sherpa.ac.uk/id/publication/8735>
dc.relation.isversionofDubé, J. B., Wang, J., Cao, H., McIntyre, A. D., Johansen, C. T., Hopkins, S. E., Stringer, R., Hosseinzadeh, S., Kennedy, B. A., Ban, M. R., Young, T. K., Connelly, P. W., Dewailly, E., Bjerregaard, P., Boyer, B. B., & Hegele, R. A. (2015). Common low density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein cholesterol in circumpolar Inuit populations. Circulation: Cardiovascular Genetics, 8(1), 100-105. https://doi.org/10.1161/circgenetics.114.000646
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCardiovascular diseases
dc.subjectGenetic variation
dc.subjectLow-density lipoprotein cholesterol
dc.titleCommon Low-Density Lipoprotein Receptor p.G116S Variant Has a Large Effect on Plasma Low-Density Lipoprotein Cholesterol in Circumpolar Inuit Populations
dc.typehttp://purl.org/coar/resource_type/c_6501 http://purl.org/coar/version/c_970fb48d4fbd8a85
dcterms.source<https://www.ahajournals.org/doi/10.1161/CIRCGENETICS.114.000646>
ual.jupiterAccesshttp://terms.library.ualberta.ca/public

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