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Erschienen in: Diabetologia 6/2005

01.06.2005 | Article

Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study

verfasst von: P. An, M. Teran-Garcia, T. Rice, T. Rankinen, S. J. Weisnagel, R. N. Bergman, R. C. Boston, S. Mandel, D. Stefanovski, A. S. Leon, J. S. Skinner, D. C. Rao, C. Bouchard

Erschienen in: Diabetologia | Ausgabe 6/2005

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Abstract

Aims/hypothesis

Impaired insulin secretion, insulin action, insulin-independent glucose effectiveness, glucose tolerance and the associated abnormalities in insulin and glucose metabolism phenotypes are precursors of type 2 diabetes. Genome-wide multipoint variance component linkage scans were carried out using 654 markers to identify quantitative trait loci for insulin sensitivity, acute insulin response to glucose, disposition index and glucose effectiveness training responses in whites and blacks in the HERITAGE Family Study.

Methods

These phenotypes were obtained from an IVGTT with the minimal model. The distributions of insulin sensitivity, acute insulin response to glucose and disposition index training responses (post-training minus baseline) were approximately normalised using a square-root transformation. All phenotypes were adjusted for the effects of age, BMI and their respective baseline values within sex and generation by race prior to linkage scans.

Results

In blacks, a promising linkage with a maximum lod score of 3.1 on 19q (54–62 Mb) for glucose effectiveness training response was found. Six interesting linkages with lod scores of at least 1.0 were found for disposition index training response in whites. They included 1p (30 Mb), 3q (152 Mb), 6p (23–42 Mb), 7q (95–96 Mb), 10p (15 Mb) and 12q (119–126 Mb).

Conclusions/interpretation

Quantitative trait loci for 20 weeks of endurance exercise training responses in insulin action and glucose metabolism phenotypes were found on chromosome 19q as well as 6p and 7q, with nominal (6p, 7q) but consistent (6p) linkages across the races.
Literatur
1.
Zurück zum Zitat Nishida Y, Tokuyama K, Nagasaka S et al (2004) Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model. Diabetes 53:315–320PubMed Nishida Y, Tokuyama K, Nagasaka S et al (2004) Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model. Diabetes 53:315–320PubMed
2.
Zurück zum Zitat Boulé NG, Weisnagel SJ Lakka TA et al (2005) Effects of exercise training on measures of glucose and insulin metabolism derived from an intravenous glucose tolerance test. The HERITAGE Family Study. Diabetes Care 28:120–126PubMed Boulé NG, Weisnagel SJ Lakka TA et al (2005) Effects of exercise training on measures of glucose and insulin metabolism derived from an intravenous glucose tolerance test. The HERITAGE Family Study. Diabetes Care 28:120–126PubMed
3.
Zurück zum Zitat Bouchard C, Rankinen T (2001) Individual differences in response to regular physical activity. Med Sci Sports Exerc 33[6 Suppl]:S446–S451CrossRefPubMed Bouchard C, Rankinen T (2001) Individual differences in response to regular physical activity. Med Sci Sports Exerc 33[6 Suppl]:S446–S451CrossRefPubMed
4.
Zurück zum Zitat An P, Hong Y, Weisnagel SJ et al (2003) Genomic scan of glucose and insulin metabolism phenotypes: the HERITAGE Family Study. Metabolism 52:246–253CrossRefPubMed An P, Hong Y, Weisnagel SJ et al (2003) Genomic scan of glucose and insulin metabolism phenotypes: the HERITAGE Family Study. Metabolism 52:246–253CrossRefPubMed
5.
Zurück zum Zitat Lakka TA, Rankinen T, Weisnagel SJ et al (2003) A quantitative trait locus on 7q31 for the changes in plasma insulin in response to exercise training: the HERITAGE Family Study. Diabetes 52:1583–1587PubMed Lakka TA, Rankinen T, Weisnagel SJ et al (2003) A quantitative trait locus on 7q31 for the changes in plasma insulin in response to exercise training: the HERITAGE Family Study. Diabetes 52:1583–1587PubMed
6.
Zurück zum Zitat Boston RC, Stefanovski D, Moate PJ et al (2003) MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 5:1003–1015CrossRefPubMed Boston RC, Stefanovski D, Moate PJ et al (2003) MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 5:1003–1015CrossRefPubMed
7.
Zurück zum Zitat Bouchard C, Leon AS, Rao DC et al (1995) The HERITAGE family study. Aims, design, and measurement protocol. Med Sci Sports Exerc 27:721–729PubMed Bouchard C, Leon AS, Rao DC et al (1995) The HERITAGE family study. Aims, design, and measurement protocol. Med Sci Sports Exerc 27:721–729PubMed
8.
Zurück zum Zitat Skinner JS, Wilmore KM, Krasnoff JB et al (2000) Adaptation to a standardized training program and changes in fitness in a large, heterogeneous population: the HERITAGE family study. Med Sci Sports Exerc 32:157–161CrossRefPubMed Skinner JS, Wilmore KM, Krasnoff JB et al (2000) Adaptation to a standardized training program and changes in fitness in a large, heterogeneous population: the HERITAGE family study. Med Sci Sports Exerc 32:157–161CrossRefPubMed
9.
Zurück zum Zitat Walton C, Godsland IF, Proudler AJ et al (1992) Evaluation of four mathematical models of glucose and insulin dynamics with analysis of effects of age and obesity. Am J Physiol 262:E755–E762PubMed Walton C, Godsland IF, Proudler AJ et al (1992) Evaluation of four mathematical models of glucose and insulin dynamics with analysis of effects of age and obesity. Am J Physiol 262:E755–E762PubMed
10.
Zurück zum Zitat Desbuquois B, Aurbach GD (1971) Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab 33:732–738PubMed Desbuquois B, Aurbach GD (1971) Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab 33:732–738PubMed
11.
Zurück zum Zitat Røder ME, Porte D Jr, Schwartz RS et al (1998) Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 83:604–608CrossRefPubMed Røder ME, Porte D Jr, Schwartz RS et al (1998) Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 83:604–608CrossRefPubMed
12.
Zurück zum Zitat Kahn SE, Leonetti DL, Prigeon RL et al (1995) Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese American men: impact of obesity—Clinical Research Center Study. J Clin Endocrinol Metab 80:1399–1406CrossRefPubMed Kahn SE, Leonetti DL, Prigeon RL et al (1995) Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese American men: impact of obesity—Clinical Research Center Study. J Clin Endocrinol Metab 80:1399–1406CrossRefPubMed
13.
Zurück zum Zitat Chagnon YC, Borecki IB, Pérusse L et al (2000) Genome-wide search for genes related to the fat-free body mass in the Quebec family study. Metabolism 49:203–207CrossRefPubMed Chagnon YC, Borecki IB, Pérusse L et al (2000) Genome-wide search for genes related to the fat-free body mass in the Quebec family study. Metabolism 49:203–207CrossRefPubMed
14.
Zurück zum Zitat Province MA, Rao DC (1995) A general purpose model and a computer program for combined segregation and path (SEGPATH): automatically creating computer program from symbolic language model specifications. Genet Epidemiol 12:203–219PubMed Province MA, Rao DC (1995) A general purpose model and a computer program for combined segregation and path (SEGPATH): automatically creating computer program from symbolic language model specifications. Genet Epidemiol 12:203–219PubMed
15.
Zurück zum Zitat Province MA, Rice T, Borecki IB (2003) A multivariate and multilocus variance components approach using structural relationships to assess quantitative trait linkage via SEGPATH. Genet Epidemiol 24:128–138CrossRefPubMed Province MA, Rice T, Borecki IB (2003) A multivariate and multilocus variance components approach using structural relationships to assess quantitative trait linkage via SEGPATH. Genet Epidemiol 24:128–138CrossRefPubMed
16.
Zurück zum Zitat Kruglyak L, Lander ES (1995) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57:439–454PubMed Kruglyak L, Lander ES (1995) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57:439–454PubMed
17.
Zurück zum Zitat Self SG, Liang KY (1987) Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under nonstandard conditions. J Am Stat Assoc 82:605–610 Self SG, Liang KY (1987) Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under nonstandard conditions. J Am Stat Assoc 82:605–610
18.
Zurück zum Zitat Rao DC, Province MA (2000) The future of path analysis, segregation analysis, and combined models for genetic dissection of complex traits. Hum Hered 50:34–42CrossRefPubMed Rao DC, Province MA (2000) The future of path analysis, segregation analysis, and combined models for genetic dissection of complex traits. Hum Hered 50:34–42CrossRefPubMed
19.
Zurück zum Zitat Loos RJ, Katzmarzyk PT, Rao DC et al (2003) Genome-wide linkage scan for the metabolic syndrome in the HERITAGE family study. J Clin Endocrinol Metab 88:5935–5943CrossRefPubMed Loos RJ, Katzmarzyk PT, Rao DC et al (2003) Genome-wide linkage scan for the metabolic syndrome in the HERITAGE family study. J Clin Endocrinol Metab 88:5935–5943CrossRefPubMed
20.
Zurück zum Zitat Aouizerat BE, Allayee H, Cantor RM et al (1999) A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11. Am J Hum Genet 65:397–412CrossRefPubMed Aouizerat BE, Allayee H, Cantor RM et al (1999) A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11. Am J Hum Genet 65:397–412CrossRefPubMed
21.
Zurück zum Zitat Pratley RE, Thompson DB, Prochazka M et al (1998) An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 101:1757–1764PubMed Pratley RE, Thompson DB, Prochazka M et al (1998) An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 101:1757–1764PubMed
22.
Zurück zum Zitat Panhuysen CI, Cupples LA, Wilson PW et al (2003) A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study. Diabetologia 46:579–587PubMed Panhuysen CI, Cupples LA, Wilson PW et al (2003) A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study. Diabetologia 46:579–587PubMed
23.
Zurück zum Zitat Watanabe RM, Ghosh S, Langefeld CD et al (2000) The Finland–United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study: II. An autosomal genome scan for diabetes-related quantitative-trait loci. Am J Hum Genet 67:1186–1200PubMed Watanabe RM, Ghosh S, Langefeld CD et al (2000) The Finland–United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study: II. An autosomal genome scan for diabetes-related quantitative-trait loci. Am J Hum Genet 67:1186–1200PubMed
24.
Zurück zum Zitat Elbein SC, Hasstedt SJ (2002) Quantitative trait linkage analysis of lipid-related traits in familial type 2 diabetes: evidence for linkage of triglyceride levels to chromosome 19q. Diabetes 51:528–535PubMed Elbein SC, Hasstedt SJ (2002) Quantitative trait linkage analysis of lipid-related traits in familial type 2 diabetes: evidence for linkage of triglyceride levels to chromosome 19q. Diabetes 51:528–535PubMed
25.
Zurück zum Zitat Mori Y, Otabe S, Dina C et al (2002) Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p. Diabetes 51:1247–1255PubMed Mori Y, Otabe S, Dina C et al (2002) Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p. Diabetes 51:1247–1255PubMed
26.
Zurück zum Zitat van Tilburg JH, Sandkuijl LA, Strengman E et al (2003) A genome-wide scan in type 2 diabetes mellitus provides independent replication of a susceptibility locus on 18p11 and suggests the existence of novel loci on 2q12 and 19q13. J Clin Endocrinol Metab 88:2223–2230CrossRefPubMed van Tilburg JH, Sandkuijl LA, Strengman E et al (2003) A genome-wide scan in type 2 diabetes mellitus provides independent replication of a susceptibility locus on 18p11 and suggests the existence of novel loci on 2q12 and 19q13. J Clin Endocrinol Metab 88:2223–2230CrossRefPubMed
27.
Zurück zum Zitat Best JD, Kahn SE, Ader M et al (1996) Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care 19:1018–1030PubMed Best JD, Kahn SE, Ader M et al (1996) Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care 19:1018–1030PubMed
28.
Zurück zum Zitat Henriksen JE, Alford F, Handberg A et al (1994) Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism. J Clin Invest 94:1196–1204PubMed Henriksen JE, Alford F, Handberg A et al (1994) Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism. J Clin Invest 94:1196–1204PubMed
29.
Zurück zum Zitat Vaag A, Henriksen JE, Beck-Nielsen H (1992) Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 89:782–788PubMed Vaag A, Henriksen JE, Beck-Nielsen H (1992) Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 89:782–788PubMed
30.
Zurück zum Zitat Groop LC, Kankuri M, Schalin-Jantti C et al (1993) Association between polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus. N Engl J Med 328:10–14CrossRefPubMed Groop LC, Kankuri M, Schalin-Jantti C et al (1993) Association between polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus. N Engl J Med 328:10–14CrossRefPubMed
31.
Zurück zum Zitat Motoyama K, Emoto M, Tahara H et al (2003) Association of muscle glycogen synthase polymorphism with insulin resistance in type 2 diabetic patients. Metabolism 52:895–899CrossRefPubMed Motoyama K, Emoto M, Tahara H et al (2003) Association of muscle glycogen synthase polymorphism with insulin resistance in type 2 diabetic patients. Metabolism 52:895–899CrossRefPubMed
32.
Zurück zum Zitat Huang X, Vaag A, Hansson M et al (2000) Impaired insulin-stimulated expression of the glycogen synthase gene in skeletal muscle of type 2 diabetic patients is acquired rather than inherited. J Clin Endocrinol 85:1584–1590CrossRef Huang X, Vaag A, Hansson M et al (2000) Impaired insulin-stimulated expression of the glycogen synthase gene in skeletal muscle of type 2 diabetic patients is acquired rather than inherited. J Clin Endocrinol 85:1584–1590CrossRef
33.
Zurück zum Zitat Chakravarthy MV, Booth FW (2004) Eating, exercise, and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 96:3–10CrossRefPubMed Chakravarthy MV, Booth FW (2004) Eating, exercise, and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 96:3–10CrossRefPubMed
34.
Zurück zum Zitat Luo TH, Zhao Y, Li G et al (2001) A genome-wide search for type II diabetes susceptibility genes in Chinese Hans. Diabetologia 44:501–506CrossRefPubMed Luo TH, Zhao Y, Li G et al (2001) A genome-wide search for type II diabetes susceptibility genes in Chinese Hans. Diabetologia 44:501–506CrossRefPubMed
36.
Zurück zum Zitat Ferré P (2004) The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53 [Suppl 1]:S43–S50PubMed Ferré P (2004) The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53 [Suppl 1]:S43–S50PubMed
37.
Zurück zum Zitat Meier JJ, Nauck MA (2004) The potential role of glucagon-like peptide 1 in diabetes. Curr Opin Investig Drugs 5:402–410PubMed Meier JJ, Nauck MA (2004) The potential role of glucagon-like peptide 1 in diabetes. Curr Opin Investig Drugs 5:402–410PubMed
38.
Zurück zum Zitat Hanson RL, Ehm MG, Pettitt DJ et al (1998) An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am J Hum Genet 63:1130–1138CrossRefPubMed Hanson RL, Ehm MG, Pettitt DJ et al (1998) An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am J Hum Genet 63:1130–1138CrossRefPubMed
Metadaten
Titel
Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study
verfasst von
P. An
M. Teran-Garcia
T. Rice
T. Rankinen
S. J. Weisnagel
R. N. Bergman
R. C. Boston
S. Mandel
D. Stefanovski
A. S. Leon
J. S. Skinner
D. C. Rao
C. Bouchard
Publikationsdatum
01.06.2005
Erschienen in
Diabetologia / Ausgabe 6/2005
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1769-4

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