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The PNPLA3-I148M Va...
The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients
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- Luukkonen, Panu K. (författare)
- Minerva Foundation Institute for Medical Research,Yale University,Helsinki University Central Hospital,University of Helsinki
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- Qadri, Sami (författare)
- Helsinki University Central Hospital,University of Helsinki,Minerva Foundation Institute for Medical Research
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- Lehtimäki, Tiina E. (författare)
- Helsinki University Central Hospital
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- Juuti, Anne (författare)
- Helsinki University Central Hospital
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- Sammalkorpi, Henna (författare)
- Helsinki University Central Hospital
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- Penttilä, Anne K. (författare)
- Helsinki University Central Hospital
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- Hakkarainen, Antti (författare)
- Helsinki University Central Hospital
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- Orho-Melander, Marju (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- Arola, Johanna (författare)
- University of Helsinki,Helsinki University Central Hospital
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- Yki-Järvinen, Hannele (författare)
- Minerva Foundation Institute for Medical Research,Helsinki University Central Hospital,University of Helsinki
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(creator_code:org_t)
- 2020-10-16
- 2021
- Engelska.
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:1, s. 300-315
- Relaterad länk:
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Abstract
Ämnesord
Stäng
- CONTEXT: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. DESIGN: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids and lipoproteins in 2 cohorts, both divided into groups based on rs738409-G allele carrier status and median HOMA-IR. SETTING: Tertiary referral center. PATIENTS: A total of 298 obese patients who underwent a liver biopsy during bariatric surgery (bariatric cohort: age 49 ± 9 years, body mass index [BMI] 43.2 ± 6.8 kg/m2), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort: age 45 ± 14 years, BMI 29.7 ± 5.7 kg/m2). MAIN OUTCOME MEASURES: Nuclear magnetic resonance profiling of plasma lipids, lipoprotein particle subclasses and their composition. RESULTS: In both cohorts, individuals carrying the PNPLA3-I148M variant had significantly higher liver fat content than noncarriers. In insulin-resistant and homozygous carriers, PNPLA3-I148M exerted a distinct antihyperlipidemic effect with decreased very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles and their constituents, and increased high-density lipoprotein particles and their constituents, compared with noncarriers. VLDL particles were smaller and LDL particles larger in PNPLA3-I148M carriers. These changes were geometrically opposite to those due to IR. PNPLA3-I148M did not have a measurable effect in patients with lower IR, and its effect was smaller albeit still significant in the less obese than in the obese cohort. CONCLUSIONS: PNPLA3-I148M confers an antiatherogenic plasma lipid profile particularly in insulin-resistant individuals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- dyslipidemia
- insulin resistance
- lipoproteins
- metabolic syndrome
- non-alcoholic fatty liver disease
- patatin-like phospholipase domain containing 3
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Luukkonen, Panu ...
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Qadri, Sami
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Lehtimäki, Tiina ...
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Juuti, Anne
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Sammalkorpi, Hen ...
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Penttilä, Anne K ...
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Hakkarainen, Ant ...
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Orho-Melander, M ...
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Arola, Johanna
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Yki-Järvinen, Ha ...
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