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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 41, Issue 4


The TNF- α Gene NcoI Polymorphism at Position –308 of the Promoter Influences Insulin Resistance, and Increases Serum Triglycerides after Postprandial Lipaemia in Familiar Obesity

Iwona Wybrańska / Malgorzata Malczewska-Malec / Sylwia Niedbal / Jerzy W. Naskalski / Aldona Dembińska-Kieć
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/CCLM.2003.076


Tumour necrosis factor alpha (TNF-α), acting as a modulator of gene expression in adipocytes, has been linked to the development of insulin resistance and obesity. The aim of this study was to investigate whether the A/G variation at position −308 in the TNFα promoter influences the body weight, insulin resistance, and postprandial lipaemia in Polish Caucasians. One hundred twenty one subjects, 38 men and 83 women, representing 40 obese families, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TNF-1 (GG) and TNF-2 (GA and AA) allele carriers were compared with respect to body mass index, fat/lean body mass composition, waist-to-hip ratio, as well as fasting lipids, glucose, leptin, and insulin fasting, and during the oral glucose tolerance test (4 points within 2 hours) and oral lipid tolerance test (OLTT; 5 points within 8 hours). The insulin sensitivity indices HOMA-IR (homeostasis model assessment of insulin resistance), ISI-COMP (whole body insulin sensitivity index), ISI-HOMA (hepatic insulin sensitivity), and DELTA (early secretory response to an oral glucose load) were calculated. We detected 64 GG, 56 GA, and 1 AA genotypes. Significant increases of insulin resistance parameters in obese female TNF-2 allele carriers were observed (significantly increased HOMA-IR and decreased ISI-HOMA, ISI-composite). The male TNF-2 carriers were characterised by significantly increased levels of triglyceride and free fatty acids during OLTT as well as fasting glucose. The A/G variation at position −308 in the promoter region of the TNF-α gene could be an important genetic factor predisposing to insulin resistance in obese women and increased levels of glucose, triglyceride, and free fatty acids in men.

About the article

Published Online: 2005-06-01

Published in Print: 2003-04-25

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 41, Issue 4, Pages 501–510, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2003.076.

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