The TNF-alpha gene NcoI polymorphism at position -308 of the promoter influences insulin resistance, and increases serum triglycerides after postprandial lipaemia in familiar obesity.
Tumour necrosis factor alpha (TNF-alpha), 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 TNF-alpha 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-alpha 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.
Department of Clinical Biochemistry, The Jagiellonian University Medical College, Kraków, Kopernika, Poland. mbwybran@cyf-kr.edu.pl
Iwona
I
Wybrańska
Małgorzata
M
Malczewska-Malec
Sylwia
S
Niedbał
Jerzy W
JW
Naskalski
Aldona
A
Dembińska-Kieć
D000328:Adult; D015992:Body Mass Index; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D019518:Postprandial Period; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; C439524:TNF protein, human; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C052380:endodeoxyribonuclease NcoI; D015252:Deoxyribonucleases, Type II Site-Specific; D005947:Glucose