Home LiteratureArticle Details
PMID: 7615786 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.

The Journal of clinical investigation ·Vol. 96 ·No. 1 ·1995-07-00 ·Pages 158-62

Norman RA, Bogardus C, Ravussin E

Abstract

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.

MeSH Terms
Adolescent Adult Body Mass Index Chromosome Mapping Female Genetic Linkage Genetic Markers Humans Indians, North American/genetics Male Middle Aged Obesity/genetics Promoter Regions, Genetic Tumor Necrosis Factor-alpha/genetics
Chemicals
Genetic Markers Tumor Necrosis Factor-alpha
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Norman R A
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
Bogardus C
Ravussin E
References (34)
34 references, click to expand
  1. Through thick and thin: wasting, obesity, and TNF alpha.
    Cell. 1993 May 21;73(4):625-7 PMID: 8500160
  2. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product.
    Hum Mol Genet. 1992 Aug;1(5):353 PMID: 1363876
  3. Large transcripts and sequence from a polymorphic 170 kb MHC region implicated in susceptibility to autoimmune disease.
    Immunogenetics. 1994;39(1):15-20 PMID: 7693583
  4. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.
    N Engl J Med. 1993 Dec 30;329(27):1988-92 PMID: 8247074
  5. The gross composition of the body.
    Adv Biol Med Phys. 1956;4:239-80 PMID: 13354513
  6. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.
    J Clin Invest. 1995 May;95(5):2409-15 PMID: 7738205
  7. Diabetes mellitus in American (Pima) Indians.
    Lancet. 1971 Jul 17;2(7716):125-8 PMID: 4104461
  8. The investigation of linkage between a quantitative trait and a marker locus.
    Behav Genet. 1972 Mar;2(1):3-19 PMID: 4157472
  9. Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells.
    Proc Natl Acad Sci U S A. 1982 Feb;79(3):912-6 PMID: 7038689
  10. Linkage between a marker locus and a quantitative trait of sibs.
    Am J Hum Genet. 1983 Mar;35(2):263-73 PMID: 6573131
  11. Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells.
    Proc Natl Acad Sci U S A. 1983 May;80(9):2743-7 PMID: 6133282
  12. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9 PMID: 6392892
  13. A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia.
    Science. 1985 Aug 30;229(4716):867-9 PMID: 3839597
  14. Familial dependence of the resting metabolic rate.
    N Engl J Med. 1986 Jul 10;315(2):96-100 PMID: 3724804
  15. Genes for the tumor necrosis factors alpha and beta are linked to the human major histocompatibility complex.
    Proc Natl Acad Sci U S A. 1986 Nov;83(22):8699-702 PMID: 3464978
  16. Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome.
    Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24 PMID: 3555974
  17. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis.
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7237-41 PMID: 3118362
  18. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8535-9 PMID: 2825194
  19. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians.
    N Engl J Med. 1988 May 12;318(19):1217-25 PMID: 3283552
  20. HLA associations with obesity.
    Hum Hered. 1989;39(3):156-64 PMID: 2591979
  21. Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level.
    J Exp Med. 1990 Feb 1;171(2):465-75 PMID: 2303781
  22. The body-mass index of twins who have been reared apart.
    N Engl J Med. 1990 May 24;322(21):1483-7 PMID: 2336075
  23. Obesity in the Pima Indians: its magnitude and relationship with diabetes.
    Am J Clin Nutr. 1991 Jun;53(6 Suppl):1543S-1551S PMID: 2031485
  24. The metabolic effects of tumor necrosis factor and other cytokines.
    Biotherapy. 1991;3(2):143-58 PMID: 2054255
  25. DNA sequence polymorphism at the human tumor necrosis factor (TNF) locus. Numerous TNF/lymphotoxin alleles tagged by two closely linked microsatellites in the upstream region of the lymphotoxin (TNF-beta) gene.
    J Immunol. 1991 Aug 1;147(3):1053-9 PMID: 1861069
  26. The genetic and environmental sources of body mass index variability: the Muscatine Ponderosity Family Study.
    Am J Hum Genet. 1991 Dec;49(6):1243-55 PMID: 1746554
  27. Genomic structure, induction, and production of TNF-alpha.
    Immunol Ser. 1992;56:3-34 PMID: 1550865
  28. Two TNF receptors.
    Immunol Today. 1992 May;13(5):151-3 PMID: 1322675
  29. A second-generation linkage map of the human genome.
    Nature. 1992 Oct 29;359(6398):794-801 PMID: 1436057
  30. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.
    Science. 1993 Jan 1;259(5091):87-91 PMID: 7678183
  31. Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface.
    Cell. 1993 Mar 26;72(6):847-56 PMID: 7916655
  32. Selective up-regulation of the 75-kDa tumor necrosis factor (TNF) receptor and its mRNA by TNF and IL-1.
    J Immunol. 1993 May 15;150(10):4346-53 PMID: 8387093
  33. Segregation analysis of fat mass and other body composition measures derived from underwater weighing.
    Am J Hum Genet. 1993 May;52(5):967-73 PMID: 8488846
  34. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions.
    Genomics. 1993 May;16(2):325-32 PMID: 8314571
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118016
Published
1995-07-00
Pages
158-62
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC185184
Subset
IM
Grants
NCRR NIH HHS · 1 P41 RR03655 · United States
External Links
PubMed source DOI: 10.1172/JCI118016 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2