Single Nucleotide Polymorphisms in the G-Protein Coupled Receptor Kinase 5 (GRK5) Gene are associated with Plasma LDL-Cholesterol Levels in Humans
Autor: | Lutz, Stefan Z., Falcenberg, Mathias, Machicao, Fausto, Peter, Andreas, Kächele, Martin, Randrianarisoa, Elko, Lehn-Stefan, Angela, Wagner, Robert, Machann, Jürgen, Schick, Fritz, Heni, Martin, Ullrich, Axel, Fritsche, Andreas, Stefan, Norbert, Häring, Hans-Ulrich, Staiger, Harald, Kantartzis, Konstantinos |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Adult
G-Protein-Coupled Receptor Kinase 5 Male Genotype Cardiovascular Abnormalities lcsh:R lcsh:Medicine Cholesterol LDL Middle Aged Carotid Intima-Media Thickness Lipids Polymorphism Single Nucleotide Article Diabetes Mellitus Type 2 Humans Insulin Female Genetic Predisposition to Disease lcsh:Q Insulin Resistance lcsh:Science |
Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Sci. Rep. 8:7745 (2018) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Genetically modified mice models suggest an important role for G-protein-coupled receptor kinase 5 (GRK5) in the pathophysiology of obesity and related disorders. We investigated whether single nucleotide polymorphisms (SNPs) in the gene encoding GRK5 affect cardiometabolic traits in humans. We genotyped 3 common SNPs in intron 1 (rs1980030, rs10466210, rs9325562) and one SNP in intron 3 (rs10886471) of GRK5 in 2332 subjects at risk for type 2 diabetes. Total- and visceral fat mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy. Insulin secretion and sensitivity were estimated during an OGTT and measured during the euglycemic, hyperinsulinemic clamp (n = 498). Carriers of the minor allele of rs10466210 and rs1980030 had higher total- and LDL-cholesterol levels (p = 0.0018 and p = 0.0031, respectively, for rs10466210; p = 0.0035 and p = 0.0081, respectively, for rs1980030), independently of gender, age, BMI and lipid-lowering drugs. The effects of rs10466210 withstood Bonferroni correction. Similar associations were observed with apolipoprotein B levels (p = 0.0034 and p = 0.0122, respectively). Carriers of the minor allele of rs10466210 additionally displayed a trend for higher intima-media thickness of the carotid artery (p = 0.075). GRK5 may represent a novel target for strategies aiming at lowering LDL-cholesterol levels and at modifying cardiovascular risk. |
Databáze: | OpenAIRE |
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