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The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation.


ABSTRACT: Non-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.The 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).The 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(?)?=?-9.9% [-14.4%;-4.0% (95% CI)], p?=?5.1×10(-5)) and fasting total cholesterol (??=?-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.Our findings suggest that the G-allele of PNPLA3 rs738409 associates with reduced fasting levels of cholesterol and triglyceride in individuals with IGR.

SUBMITTER: Krarup NT 

PROVIDER: S-EPMC3390392 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation.

Krarup Nikolaj Thure NT   Krarup Nikolaj Thure NT   Grarup Niels N   Banasik Karina K   Friedrichsen Martin M   Færch Kristine K   Sandholt Camilla Helene CH   Jørgensen Torben T   Poulsen Pernille P   Witte Daniel Rinse DR   Vaag Allan A   Sørensen Thorkild T   Pedersen Oluf O   Hansen Torben T  

PloS one 20120705 7


<h4>Background and aim</h4>Non-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.<h4>Methods</h4>The rs738409 variant was genotyped in the population-based Inter99 cohort examined by an oral glucose-tolerance test, and a  ...[more]

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