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Novel association of TM6SF2 rs58542926 genotype with increased serum tyrosine levels and decreased apoB-100 particles in Finns.


ABSTRACT: A glutamate-to-lysine variant (rs58542926-T) in transmembrane 6 superfamily member 2 (TM6SF2) is associated with increased fatty liver disease and diabetes in conjunction with decreased cardiovascular disease risk. To identify mediators of the effects of TM6SF2, we tested for associations between rs58542926-T and serum lipoprotein/metabolite measures in cross-sectional data from nondiabetic statin-naïve participants. We identified independent associations between rs58542926-T and apoB-100 particles (? = -0.057 g/l, P = 1.99 × 10-14) and tyrosine levels (? = 0.0020 mmol/l, P = 1.10 × 10-8), controlling for potential confounders, in 6,929 Finnish men. The association between rs58542926-T and apoB-100 was confirmed in an independent sample of 2,196 Finnish individuals from the FINRISK study (?replication = -0.029, Preplication = 0.029). Secondary analyses demonstrated an rs58542926-T dose-dependent decrease in particle concentration, cholesterol, and triglyceride (TG) content for VLDL and LDL particles (P < 0.001 for all). No significant associations between rs58542926-T and HDL measures were observed. TM6SF2 SNP rs58542926-T and tyrosine levels were associated with increased incident T2D risk in both METSIM and FINRISK. Decreased liver production/secretion of VLDL, decreased cholesterol and TGs in VLDL/LDL particles in serum, and increased tyrosine levels identify possible mechanisms by which rs58542926-T exerts its effects on increasing risk of fatty liver disease, decreasing cardiovascular disease, and increasing diabetes risk, respectively.

SUBMITTER: Kim DS 

PROVIDER: S-EPMC5496043 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Novel association of <i>TM6SF2</i> rs58542926 genotype with increased serum tyrosine levels and decreased apoB-100 particles in Finns.

Kim Daniel Seung DS   Jackson Anne U AU   Li Yatong K YK   Stringham Heather M HM   Kuusisto Johanna J   Kangas Antti J AJ   Soininen Pasi P   Ala-Korpela Mika M   Burant Charles F CF   Salomaa Veikko V   Boehnke Michael M   Laakso Markku M   Speliotes Elizabeth K EK  

Journal of lipid research 20170524 7


A glutamate-to-lysine variant (rs58542926-T) in transmembrane 6 superfamily member 2 (<i>TM6SF2</i>) is associated with increased fatty liver disease and diabetes in conjunction with decreased cardiovascular disease risk. To identify mediators of the effects of <i>TM6SF2</i>, we tested for associations between rs58542926-T and serum lipoprotein/metabolite measures in cross-sectional data from nondiabetic statin-naïve participants. We identified independent associations between rs58542926-T and a  ...[more]

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