PMID- 11319665 OWN - NLM STAT- MEDLINE DCOM- 20011025 LR - 20221207 VI - 25 IP - 4 DP - 2001 Apr TI - Tumor necrosis factor-alpha--308 G/A polymorphism in obese Caucasians. PG - 581-5 AB - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking region of the TNF-alpha gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS: We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ernahrung Geschwister)- Study for the TNF-alpha-G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (GG, n=118; GA, n=53; AA, n=5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3-31.9 kg/m2; III, 31.9-36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with -308A allele carriers having a higher BMI than G allele carriers (P=0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our findings support the hypothesis that the G-308A polymophism of the TNF-alpha gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians. FAU - Brand, E AU - Brand E AD - Department of Internal Medicine, Division of Endocrinology and Nephrology, Universitatsklinkum Benjamin Franklin, Freie Universitat Berlin, Berlin, Germany. FAU - Schorr, U AU - Schorr U FAU - Kunz, I AU - Kunz I FAU - Kertmen, E AU - Kertmen E FAU - Ringel, J AU - Ringel J FAU - Distler, A AU - Distler A FAU - Sharma, A M AU - Sharma AM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Int J Obes Relat Metab Disord JT - International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity JID - 9313169 RN - 0 (Genetic Markers) RN - 0 (Leptin) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Alleles MH - Body Composition MH - Female MH - Gene Frequency MH - Genetic Markers MH - Genotype MH - Glucose Tolerance Test MH - Humans MH - Insulin Resistance MH - Leptin MH - Male MH - Middle Aged MH - Obesity/*genetics MH - *Polymorphism, Genetic MH - Tumor Necrosis Factor-alpha/*genetics MH - White People/*genetics EDAT- 2001/04/25 10:00 MHDA- 2001/10/26 10:01 CRDT- 2001/04/25 10:00 PHST- 2000/03/20 00:00 [received] PHST- 2000/10/02 00:00 [revised] PHST- 2000/11/14 00:00 [accepted] PHST- 2001/04/25 10:00 [pubmed] PHST- 2001/10/26 10:01 [medline] PHST- 2001/04/25 10:00 [entrez] AID - 10.1038/sj.ijo.0801576 [doi] PST - ppublish SO - Int J Obes Relat Metab Disord. 2001 Apr;25(4):581-5. doi: 10.1038/sj.ijo.0801576.