Novel association of TM6SF2 rs58542926 genotype with increased serum tyrosine levels and decreased apoB-100 particles in Finns.
J Lipid Res
; 58(7): 1471-1481, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28539357
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 (ß = -0.057 g/l, P = 1.99 × 10-14) and tyrosine levels (ß = 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 (ßreplication = -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.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tirosina
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Polimorfismo de Nucleótido Simple
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Apolipoproteína B-100
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Genotipo
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Proteínas de la Membrana
Tipo de estudio:
Observational_studies
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Prevalence_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
País como asunto:
Europa
Idioma:
En
Año:
2017
Tipo del documento:
Article