The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation |
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Authors: | Nikolaj Thure Krarup Niels Grarup Karina Banasik Martin Friedrichsen Kristine Færch Camilla Helene Sandholt Torben Jørgensen Pernille Poulsen Daniel Rinse Witte Allan Vaag Thorkild Sørensen Oluf Pedersen Torben Hansen |
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Institution: | The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. nikolaj.krarup@sund.ku.dk |
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Abstract: | Background and AimNon-alcoholic fatty liver disease (NAFLD) is a common condition, associated with hepatic insulin resistance and the metabolic syndrome including hyperglycaemia and dyslipidemia. We aimed at studying the potential impact of the NAFLD-associated PNPLA3 rs738409 G-allele on NAFLD-related metabolic traits in hyperglycaemic individuals.MethodsThe rs738409 variant was genotyped in the population-based Inter99 cohort examined by an oral glucose-tolerance test, and a combined study-sample consisting of 192 twins (96 twin pairs) and a sub-set of the Inter99 population (n?=?63) examined by a hyperinsulinemic euglycemic clamp (n
total?=?255). In Inter99, we analyzed associations of rs738409 with components of the WHO-defined metabolic syndrome (n?=?5,847) and traits related to metabolic disease (n?=?5,663). In the combined study sample we elucidated whether the rs738409 G-allele altered hepatic or peripheral insulin sensitivity. Study populations were divided into individuals with normal glucose-tolerance (NGT) and with impaired glucose regulation (IGR).ResultsThe case-control study showed no associations with components of the metabolic syndrome or the metabolic syndrome. Among 1,357 IGR individuals, the rs738409 G-allele associated with decreased fasting serum triglyceride levels (per allele effect(β)?=??9.9% ?14.4%;?4.0% (95% CI)], p?=?5.1×10?5) and fasting total cholesterol (β?=??0.2 mmol/l ?0.3;?0.01 mmol/l(95% CI)], p?=?1.5×10?4). Meta-analyses showed no impact on hepatic or peripheral insulin resistance in carriers of the rs738409 G-allele.ConclusionOur findings suggest that the G-allele of PNPLA3 rs738409 associates with reduced fasting levels of cholesterol and triglyceride in individuals with IGR. |
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