Skip to main content
Erschienen in: Diabetologia 9/2007

01.09.2007 | Article

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

verfasst von: B. Benyamin, T. I. A. Sørensen, K. Schousboe, M. Fenger, P. M. Visscher, K. O. Kyvik

Erschienen in: Diabetologia | Ausgabe 9/2007

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic and environmental factors influencing this cluster in a general population of twin pairs.

Materials and methods

A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry.

Results

All endophenotypes showed moderate to high heritability (0.31–0.69) and small common environmental variance (0.05–0.21). In general, genetic and phenotypic correlations between the endophenotypes were strong only within sets of physiologically similar endophenotypes, but weak to moderate for other pairs of endophenotypes. However, moderate correlations between insulin resistance indices and either obesity-related endophenotypes or triacylglycerol levels indicated that some common genetic backgrounds are shared between those components.

Conclusions/interpretation

We demonstrated that, in a general population, the endophenotypes associated with the metabolic syndrome apparently do not share a substantial common genetic or familial environmental background.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Zurück zum Zitat Roche HM, Phillips C, Gibney MJ (2005) The metabolic syndrome: the crossroads of diet and genetics. Proc Nutr Soc 64:371–377PubMedCrossRef Roche HM, Phillips C, Gibney MJ (2005) The metabolic syndrome: the crossroads of diet and genetics. Proc Nutr Soc 64:371–377PubMedCrossRef
3.
Zurück zum Zitat Shaw DI, Hall WL, Williams CM (2005) Metabolic syndrome: what is it and what are the implications? Proc Nutr Soc 64:349–357PubMedCrossRef Shaw DI, Hall WL, Williams CM (2005) Metabolic syndrome: what is it and what are the implications? Proc Nutr Soc 64:349–357PubMedCrossRef
4.
Zurück zum Zitat Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA (2002) Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 156:1070–1077PubMedCrossRef Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA (2002) Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 156:1070–1077PubMedCrossRef
5.
Zurück zum Zitat Girman CJ, Dekker JM, Rhodes T et al (2005) An exploratory analysis of criteria for the metabolic syndrome and its prediction of long-term cardiovascular outcomes: the Hoorn Study. Am J Epidemiol 162:438–447PubMedCrossRef Girman CJ, Dekker JM, Rhodes T et al (2005) An exploratory analysis of criteria for the metabolic syndrome and its prediction of long-term cardiovascular outcomes: the Hoorn Study. Am J Epidemiol 162:438–447PubMedCrossRef
6.
Zurück zum Zitat Sundstrom J, Riserus U, Byberg L, Zethelius B, Lithell H, Lind L (2006) Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study. BMJ 332:878–882PubMedCrossRef Sundstrom J, Riserus U, Byberg L, Zethelius B, Lithell H, Lind L (2006) Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study. BMJ 332:878–882PubMedCrossRef
7.
Zurück zum Zitat Cameron AJ, Shaw JE, Zimmet PZ (2004) The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin North Am 33:351–375PubMedCrossRef Cameron AJ, Shaw JE, Zimmet PZ (2004) The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin North Am 33:351–375PubMedCrossRef
8.
Zurück zum Zitat Ford ES, Giles WH (2003) A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 26:575–581PubMedCrossRef Ford ES, Giles WH (2003) A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 26:575–581PubMedCrossRef
9.
Zurück zum Zitat Freeman MS, Mansfield MW, Barrett JH, Grant PJ (2002) Heritability of features of insulin resistance syndrome in a community-based study of healthy families. Diabet Med 19:994–999PubMedCrossRef Freeman MS, Mansfield MW, Barrett JH, Grant PJ (2002) Heritability of features of insulin resistance syndrome in a community-based study of healthy families. Diabet Med 19:994–999PubMedCrossRef
10.
Zurück zum Zitat Li JKY, Ng MCY, So WY et al (2006) Phenotypic and genetic clustering of the metabolic syndrome in Chinese families with type 2 diabetes mellitus. Diabetes Metab Res Rev 22:46–52PubMedCrossRef Li JKY, Ng MCY, So WY et al (2006) Phenotypic and genetic clustering of the metabolic syndrome in Chinese families with type 2 diabetes mellitus. Diabetes Metab Res Rev 22:46–52PubMedCrossRef
11.
Zurück zum Zitat Lin H-F, Boden-Albala B, Juo SH, Park N, Rundek T, Sacco RL (2005) Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study. Diabetologia 48:2006–2012PubMedCrossRef Lin H-F, Boden-Albala B, Juo SH, Park N, Rundek T, Sacco RL (2005) Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study. Diabetologia 48:2006–2012PubMedCrossRef
12.
Zurück zum Zitat Martin LJ, North KE, Dyer T, Blangero J, Comuzzie AG, Williams J (2003) Phenotypic, genetic, and genome-wide structure in the metabolic syndrome. BMC Genet 4(Suppl.1):S95PubMedCrossRef Martin LJ, North KE, Dyer T, Blangero J, Comuzzie AG, Williams J (2003) Phenotypic, genetic, and genome-wide structure in the metabolic syndrome. BMC Genet 4(Suppl.1):S95PubMedCrossRef
13.
Zurück zum Zitat Poulsen P, Vaag A, Kyvik K, Beck-Nielsen H (2001) Genetic versus environmental aetiology of the metabolic syndrome among male and female twins. Diabetologia 44:537–543PubMedCrossRef Poulsen P, Vaag A, Kyvik K, Beck-Nielsen H (2001) Genetic versus environmental aetiology of the metabolic syndrome among male and female twins. Diabetologia 44:537–543PubMedCrossRef
14.
Zurück zum Zitat Schousboe K, Visscher PM, Henriksen JE, Hopper JL, Sørensen TI, Kyvik KO (2003) Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion. Diabetologia 46:1276–1283PubMedCrossRef Schousboe K, Visscher PM, Henriksen JE, Hopper JL, Sørensen TI, Kyvik KO (2003) Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion. Diabetologia 46:1276–1283PubMedCrossRef
15.
Zurück zum Zitat Henkin L, Bergman RN, Bowden DW et al (2003) Genetic epidemiology of insulin resistance and visceral adiposity: the IRAS Family Study design and methods. Ann Epidemiol 13:211–217PubMedCrossRef Henkin L, Bergman RN, Bowden DW et al (2003) Genetic epidemiology of insulin resistance and visceral adiposity: the IRAS Family Study design and methods. Ann Epidemiol 13:211–217PubMedCrossRef
16.
Zurück zum Zitat Samaras K, Nguyen TV, Jenkins AB et al (1999) Clustering of insulin resistance, total and central abdominal fat: same genes or same environment? Twin Res 2:218–225PubMedCrossRef Samaras K, Nguyen TV, Jenkins AB et al (1999) Clustering of insulin resistance, total and central abdominal fat: same genes or same environment? Twin Res 2:218–225PubMedCrossRef
17.
Zurück zum Zitat Hong Y, Pedersen NL, Brismar K, Faire UD (1997) Genetic and environmental architecture of the features of the insulin-resistance syndrome. Am J Hum Genet 60:143–152PubMed Hong Y, Pedersen NL, Brismar K, Faire UD (1997) Genetic and environmental architecture of the features of the insulin-resistance syndrome. Am J Hum Genet 60:143–152PubMed
18.
Zurück zum Zitat Nelson TL, Vogler GP, Pedersen NL, Hong Y, Miles TP (2000) Genetic and environmental influences on body fat distribution, fasting insulin levels and CVD: are the influences shared? Twin Res 3:43–50PubMedCrossRef Nelson TL, Vogler GP, Pedersen NL, Hong Y, Miles TP (2000) Genetic and environmental influences on body fat distribution, fasting insulin levels and CVD: are the influences shared? Twin Res 3:43–50PubMedCrossRef
19.
Zurück zum Zitat Tregouet DA, Herbeth B, Juhan-Vague I, Siest G, Ducimetiere P, Tiret L (1999) Bivariate familial correlation analysis of quantitative traits by use of estimating equation: application to a familial analysis of the insulin resistance syndrome. Genet Epidemiol 16:69–83PubMedCrossRef Tregouet DA, Herbeth B, Juhan-Vague I, Siest G, Ducimetiere P, Tiret L (1999) Bivariate familial correlation analysis of quantitative traits by use of estimating equation: application to a familial analysis of the insulin resistance syndrome. Genet Epidemiol 16:69–83PubMedCrossRef
20.
Zurück zum Zitat Perusse L, Rice T, Despres JP, Rao DC, Bouchard C (1997) Cross-trait familial resemblance for body fat and blood lipids: familial correlations in the Quebec Family Study. Arterioscler Thromb Vasc Biol 17:3270–3277PubMed Perusse L, Rice T, Despres JP, Rao DC, Bouchard C (1997) Cross-trait familial resemblance for body fat and blood lipids: familial correlations in the Quebec Family Study. Arterioscler Thromb Vasc Biol 17:3270–3277PubMed
21.
Zurück zum Zitat Rainwater DL, Mitchell BD, Mahaney MC, Haffner SM (1997) Genetic relationship between measures of HDL phenotypes and insulin concentrations. Arterioscler Thromb Vasc Biol 17:3414–3419PubMed Rainwater DL, Mitchell BD, Mahaney MC, Haffner SM (1997) Genetic relationship between measures of HDL phenotypes and insulin concentrations. Arterioscler Thromb Vasc Biol 17:3414–3419PubMed
22.
Zurück zum Zitat Kahn R, Buse J, Ferrannini E, Stern M (2005) The metabolic syndrome: time for a critical appraisal. Joint statement from the American Association and the European Association for the Study of Diabetes. Diabetes Care 28:2289–2304PubMedCrossRef Kahn R, Buse J, Ferrannini E, Stern M (2005) The metabolic syndrome: time for a critical appraisal. Joint statement from the American Association and the European Association for the Study of Diabetes. Diabetes Care 28:2289–2304PubMedCrossRef
23.
Zurück zum Zitat Schousboe K, Visscher PM, Erbas B et al (2004) Twin study of genetic and environmental influences on adult body size, shape and composition. Int J Obes 28:39–48CrossRef Schousboe K, Visscher PM, Erbas B et al (2004) Twin study of genetic and environmental influences on adult body size, shape and composition. Int J Obes 28:39–48CrossRef
24.
Zurück zum Zitat Hansen T, Drivsholm T, Urhammer SA et al (2007) The BIGTT test: a novel test for simultaneous measurement of pancreatic beta-cell function, insulin sensitivity, and glucose tolerance. Diabetes Care 30:257–262PubMedCrossRef Hansen T, Drivsholm T, Urhammer SA et al (2007) The BIGTT test: a novel test for simultaneous measurement of pancreatic beta-cell function, insulin sensitivity, and glucose tolerance. Diabetes Care 30:257–262PubMedCrossRef
25.
Zurück zum Zitat Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
28.
Zurück zum Zitat Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ (1993) A test of the equal-environment assumption in twin studies of psychiatric illness. Behav Genet 23:21–27PubMedCrossRef Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ (1993) A test of the equal-environment assumption in twin studies of psychiatric illness. Behav Genet 23:21–27PubMedCrossRef
29.
Zurück zum Zitat Scarr S (1968) Environmental bias in twin studies. Eugen Q 15:34–40PubMed Scarr S (1968) Environmental bias in twin studies. Eugen Q 15:34–40PubMed
30.
Zurück zum Zitat Edwards KL, Newman B, Mayer E, Selby JV, Krauss RM, Austin MA (1997) Heritability of factors of the insulin resistance syndrome in women twins. Genet Epidemiol 14:241–253PubMedCrossRef Edwards KL, Newman B, Mayer E, Selby JV, Krauss RM, Austin MA (1997) Heritability of factors of the insulin resistance syndrome in women twins. Genet Epidemiol 14:241–253PubMedCrossRef
31.
Zurück zum Zitat Mitchell BD, Kammerer CM, Mahaney MC et al (1996) Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. Arterioscler Thromb Vasc Biol 16:281–288PubMed Mitchell BD, Kammerer CM, Mahaney MC et al (1996) Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. Arterioscler Thromb Vasc Biol 16:281–288PubMed
32.
Zurück zum Zitat An P, Freedman BI, Hanis CL et al (2005) Genome-wide linkage scans for fasting glucose, insulin, and insulin resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program. Diabetes 54:909–914PubMedCrossRef An P, Freedman BI, Hanis CL et al (2005) Genome-wide linkage scans for fasting glucose, insulin, and insulin resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program. Diabetes 54:909–914PubMedCrossRef
33.
Zurück zum Zitat Kissebah AH, Sonnenberg GE, Myklebust J et al (2000) Quantitative trait loci on chromosome 3 and 17 influence phenotypes of the metabolic syndrome. PNAS 97:14478–14483PubMedCrossRef Kissebah AH, Sonnenberg GE, Myklebust J et al (2000) Quantitative trait loci on chromosome 3 and 17 influence phenotypes of the metabolic syndrome. PNAS 97:14478–14483PubMedCrossRef
34.
Zurück zum Zitat Rich SS, Bowden DW, Haffner SM et al (2005) A genome scan for fasting insulin and fasting glucose identifies a quantitative trait locus on chromosome 17p: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes 54:290–295PubMedCrossRef Rich SS, Bowden DW, Haffner SM et al (2005) A genome scan for fasting insulin and fasting glucose identifies a quantitative trait locus on chromosome 17p: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes 54:290–295PubMedCrossRef
35.
Zurück zum Zitat Shearman AM, Ordovas JM, Cupples LA et al (2000) Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham Study. Hum Mol Genet 9:1315–1320PubMedCrossRef Shearman AM, Ordovas JM, Cupples LA et al (2000) Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham Study. Hum Mol Genet 9:1315–1320PubMedCrossRef
36.
Zurück zum Zitat Jowett JB, Elliot KS, Curran JE et al (2004) Genetic variation in BEACON influences quantitative variation in metabolic syndrome-related phenotypes. Diabetes 53:2467–2472PubMedCrossRef Jowett JB, Elliot KS, Curran JE et al (2004) Genetic variation in BEACON influences quantitative variation in metabolic syndrome-related phenotypes. Diabetes 53:2467–2472PubMedCrossRef
37.
Zurück zum Zitat Goldin LR, Camp NJ, Keen KJ et al (2003) Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from genetic analysis workshop 13. Genet Epidemiol 25:S78–S89PubMedCrossRef Goldin LR, Camp NJ, Keen KJ et al (2003) Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from genetic analysis workshop 13. Genet Epidemiol 25:S78–S89PubMedCrossRef
38.
Zurück zum Zitat Loos RJF, Katzmarzyk PT, Rao DC et al (2003) Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study. J Clin Endocrinol Metab 88:5935–5943PubMedCrossRef Loos RJF, Katzmarzyk PT, Rao DC et al (2003) Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study. J Clin Endocrinol Metab 88:5935–5943PubMedCrossRef
39.
Zurück zum Zitat McQueen MB, Bertram L, Rimm EB, Blacker D, Santangelo SL (2003) A QTL genome scan of the metabolic syndrome and its component traits. BMC Genet 4(Suppl.1):S96PubMedCrossRef McQueen MB, Bertram L, Rimm EB, Blacker D, Santangelo SL (2003) A QTL genome scan of the metabolic syndrome and its component traits. BMC Genet 4(Suppl.1):S96PubMedCrossRef
40.
Zurück zum Zitat Ng MCY, So WY, Lam VKL et al (2004) Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus in chromosome 1q21–q25. Diabetes 53:2676–2683PubMedCrossRef Ng MCY, So WY, Lam VKL et al (2004) Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus in chromosome 1q21–q25. Diabetes 53:2676–2683PubMedCrossRef
41.
Zurück zum Zitat Tang W, Miller MB, Rich SS et al (2003) Linkage analysis of a composite factor for the multiple metabolic syndrome. Diabetes 52:2840–2847PubMedCrossRef Tang W, Miller MB, Rich SS et al (2003) Linkage analysis of a composite factor for the multiple metabolic syndrome. Diabetes 52:2840–2847PubMedCrossRef
Metadaten
Titel
Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?
verfasst von
B. Benyamin
T. I. A. Sørensen
K. Schousboe
M. Fenger
P. M. Visscher
K. O. Kyvik
Publikationsdatum
01.09.2007
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 9/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0758-1

Weitere Artikel der Ausgabe 9/2007

Diabetologia 9/2007 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.