Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.
Because tumor necrosis factor-alpha (TNF-alpha) expression is increased in adipose tissue of both rodent models of obesity and obese humans, it has been considered as a candidate gene for obesity. Pima Indians were scored for genotypes at three polymorphic dinucleotide repeat loci (markers) near the gene TNF-alpha at 6p21.3. In a sib-pair linkage analysis, percent body fat, as measured by hydrostatic weighing, was linked (304 sib-pairs, P = 0.002) to the marker closest (10 kb) to TNF-alpha. The same marker was associated (P = 0.01) by analysis of variance with BMI. To search for possible DNA variants in TNF-alpha that contribute to obesity, single stranded conformational polymorphism analysis was performed from 20 obese and 20 lean subjects. Primer pairs were designed for the entire TNF-alpha protein coding region and part of the promoter. Only a single polymorphism located in the promoter region was detected. No association could be demonstrated between alleles at this polymorphism and percent body fat. We conclude that the linkage of TNF-alpha to obesity might be due to a sequence variant undetected in TNF-alpha or due to a variant in some other closely linked gene.
Norman
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RA
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
Bogardus
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C
Ravussin
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E
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha