Skip to main content
SpringerLink
Log in

Association of Interleukin-1 gene polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the Interleukin-1 (IL-1) gene family are associated with central obesity and metabolic syndrome in a coronary heart disease population. The IL-1α C-889T (rs1800587) and IL-1β +3954 (rs1143634) SNPs were studied in a Western Australian coronary heart disease (CHD) population (N = 556). Subjects who were TT homozygous at either SNP had larger waist circumference (IL-1α: 1.8 cm greater, P = 0.04; IL-1β: 4 cm greater, P = 0.0004) compared with major allele homozygotes. Individuals with two copies of the IL-1α:IL-1β T:T haplotype had greater waist circumference (4.7 cm greater, P = 0.0001) compared to other haplotypes. There was a significant interaction between the IL-1β SNP and BMI level on waist circumference (P = 0.01). When the cohort was stratified by median BMI, TT carriers for IL-1β with above median BMI had greater waist circumference (6.1 cm greater, P = 0.007) compared to baseline carriers, whilst no significant association was seen in the below median group. Similarly, when the cohort was stratified by median fibrinogen level (IL-1α interaction P = 0.01; IL-1β interaction P = 0.04), TT carriers for both SNPs in the above median fibrinogen group had greater waist circumference (IL-1α 2.7 cm greater, P = 0.007; IL-1β 3.3 cm greater, P = 0.003) compared with major allele homozygotes. This association was not seen in the below median group. Also, we found a trend of increased metabolic syndrome for IL-1β TT homozygotes (P = 0.07). In conclusion, our findings suggest that in a CHD population IL-1 gene polymorphisms may be involved in increased central obesity, and the genetic influences are more evident among patients who have a higher level of obesity or inflammatory markers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A (2006) Inflammatory process in type 2 diabetes: the role of cytokines. Ann N Y Acad Sci 1084:89–117

    Article  PubMed  CAS  Google Scholar 

  • Bruun JM, Pedersen SB, Kristensen K, Richelsen B (2002) Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. Mol Cell Endocrinol 190:91–99

    Article  PubMed  CAS  Google Scholar 

  • Carter KW, McCaskie PA, Palmer LJ (2006) JLIN: a java based linkage disequilibrium plotter. BMC Bioinformatics 7:60

    Article  PubMed  Google Scholar 

  • Chida D, Osaka T, Hashimoto O, Iwakura Y (2006) Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice. Diabetes 55:971–977

    Article  PubMed  CAS  Google Scholar 

  • Di Renzo L, Bigioni M, Del Gobbo V, Premrov MG, Barbini U, Di Lorenzo N, De Lorenzo A (2007) Interleukin-1 (IL-1) receptor antagonist gene polymorphism in normal weight obese syndrome: relationship to body composition and IL-1 alpha and beta plasma levels. Pharmacol Res 55:131–138

    Article  PubMed  CAS  Google Scholar 

  • Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147

    PubMed  CAS  Google Scholar 

  • Dominici R, Cattaneo M, Malferrari G, Archi D, Mariani C, Grimaldi LM, Biunno I (2002) Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1 alpha. Immunogenetics 54:82–86

    Article  PubMed  CAS  Google Scholar 

  • Engels EA, Wu X, Gu J, Dong Q, Liu J, Spitz MR (2007) Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer. Cancer Res 67:6520–6527

    Article  PubMed  CAS  Google Scholar 

  • Garcia MC, Wernstedt I, Berndtsson A, Enge M, Bell M, Hultgren O, Horn M, Ahren B, Enerback S, Ohlsson C, Wallenius V, Jansson JO (2006) Mature-onset obesity in interleukin-1 receptor I knockout mice. Diabetes 55:1205–1213

    Article  PubMed  CAS  Google Scholar 

  • Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752

    Article  PubMed  Google Scholar 

  • Ihaka R, Gentleman R (1996) R: a language for data analysis and graphics. J Comput Graph Stat 5:299–314

    Article  Google Scholar 

  • Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF (2007) Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148:241–251

    Article  PubMed  CAS  Google Scholar 

  • de Jongh CM, Khrenova L, Kezic S, Rustemeyer T, Verberk MM, John SM (2008) Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1 alpha concentration in uninvolved skin of patients with chronic irritant contact dermatitis. Contact Dermatitis 58:263–268

    Article  PubMed  Google Scholar 

  • Juge-Aubry CE, Somm E, Chicheportiche R, Burger D, Pernin A, Cuenod-Pittet B, Quinodoz P, Giusti V, Dayer JM, Meier CA (2004) Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue. J Clin Endocrinol Metab 89:2652–2658

    Article  PubMed  CAS  Google Scholar 

  • Lorenzo C, Serrano-Rios M, Martinez-Larrad MT, Gonzalez-Sanchez JL, Seclen S, Villena A, Gonzalez-Villalpando C, Williams K, Haffner SM (2006) Geographic variations of the International Diabetes Federation and the National Cholesterol Education Program-Adult Treatment Panel III definitions of the metabolic syndrome in nondiabetic subjects. Diabetes Care 29:685–691

    Article  PubMed  Google Scholar 

  • McCaskie PA, Cadby G, Hung J, McQuillan BM, Chapman CM, Carter KW, Thompson PL, Palmer LJ, Beilby JP (2006) The C-480T hepatic lipase polymorphism is associated with HDL-C but not with risk of coronary heart disease. Clin Genet 70:114–121

    Article  PubMed  CAS  Google Scholar 

  • McCaskie PA, Carter KW, Palmer LJ (2007) SimHap: a comprehensive modelling framework and a simulation-based approach to haplotypic analysis of population-based data. http://www.genepi.org.au/simhap

  • McQuillan BM, Beilby JP, Nidorf M, Thompson PL, Hung J (1999) Hyperhomocysteinemia but not the C677T mutation of methylenetetrahydrofolate reductase is an independent risk determinant of carotid wall thickening. The Perth Carotid Ultrasound Disease Assessment Study (CUDAS). Circulation 99:2383–2388

    PubMed  CAS  Google Scholar 

  • Miller M, Rhyne J, Chen H, Beach V, Ericson R, Luthra K, Dwivedi M, Misra A (2007) APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome. Arch Med Res 38:444–451

    Article  PubMed  CAS  Google Scholar 

  • Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J (1992) A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 22:396–402

    Article  PubMed  CAS  Google Scholar 

  • Qatanani M, Lazar MA (2007) Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev 21:1443–1455

    Article  PubMed  CAS  Google Scholar 

  • Salmenniemi U, Ruotsalainen E, Pihlajamaki J, Vauhkonen I, Kainulainen S, Punnonen K, Vanninen E, Laakso M (2004) Multiple abnormalities in glucose and energy metabolism and coordinated changes in levels of adiponectin, cytokines, and adhesion molecules in subjects with metabolic syndrome. Circulation 110:3842–3848

    Article  PubMed  CAS  Google Scholar 

  • Shen J, Arnett DK, Peacock JM, Parnell LD, Kraja A, Hixson JE, Tsai MY, Lai CQ, Kabagambe EK, Straka RJ, Ordovas JM (2007) Interleukin1beta genetic polymorphisms interact with polyunsaturated fatty acids to modulate risk of the metabolic syndrome. J Nutr 137:1846–1851

    PubMed  CAS  Google Scholar 

  • Somm E, Cettour-Rose P, Asensio C, Charollais A, Klein M, Theander-Carrillo C, Juge-Aubry CE, Dayer JM, Nicklin MJ, Meda P, Rohner-Jeanrenaud F, Meier CA (2006) Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents. Diabetologia 49:387–393

    Article  PubMed  CAS  Google Scholar 

  • Strandberg L, Lorentzon M, Hellqvist A, Nilsson S, Wallenius V, Ohlsson C, Jansson JO (2006) Interleukin-1 system gene polymorphisms are associated with fat mass in young men. J Clin Endocrinol Metab 91:2749–2754

    Article  PubMed  CAS  Google Scholar 

  • Thalmann S, Meier CA (2007) Local adipose tissue depots as cardiovascular risk factors. Cardiovasc Res 75:690–701

    Article  PubMed  CAS  Google Scholar 

  • Um JY, Lee KM, Kim HM (2004) Polymorphism of interleukin-1 receptor antagonist gene and obesity. Clin Chim Acta 340:173–177

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the assistance of the Western Australian Genetic Epidemiology Resource and the Western Australian DNA Bank (both National Health and Medical Research Council of Australia National Enabling Facilities). The work was supported by the National Health and Medical Research Council of Australia (NHMRC) Project Grant 211980. KWC was supported by the Australian Research Council Discovery Project DP0663247. BLP was supported by a Howard Florey Postdoctoral Fellowship from the NHMRC. The authors thank the participants of the CUPID study.

Author information

Authors and Affiliations

  1. Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Perth, WA, Australia

    Kim W. Carter, Brenda L. Powell & Steven Wiltshire

  2. Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia, Perth, WA, Australia

    Joseph Hung, Brendan M. McQuillan & Peter L. Thompson

  3. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia

    Joseph Hung, Brendan T. X. Foo, Yuen C. Leow, Brendan M. McQuillan & Peter L. Thompson

  4. Clinical Biochemistry, PathWest Laboratory Medicine Western Australia, Perth, WA, Australia

    Michelle Jennens & John P. Beilby

  5. Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Perth, WA, Australia

    Pamela A. McCaskie & Lyle J. Palmer

  6. School of Mathematics and Statistics, University of Western Australia, Perth, WA, Australia

    Pamela A. McCaskie

  7. School of Surgery and Pathology, University of Western Australia, Perth, WA, Australia

    John P. Beilby

  8. Telethon Institute for Child Health Research, UWA Centre for Child Health Research, University of Western Australia, 100 Roberts Rd, Subiaco, WA, 6008, Australia

    Kim W. Carter

Authors
  1. Kim W. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brenda L. Powell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven Wiltshire
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brendan T. X. Foo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuen C. Leow
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brendan M. McQuillan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michelle Jennens
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pamela A. McCaskie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peter L. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. John P. Beilby
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lyle J. Palmer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kim W. Carter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carter, K.W., Hung, J., Powell, B.L. et al. Association of Interleukin-1 gene polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population. Hum Genet 124, 199–206 (2008). https://doi.org/10.1007/s00439-008-0540-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-008-0540-6

Keywords

Search

Navigation