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Published in: Diabetologia 10/2004

01-10-2004 | Article

Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects

Authors: K. N. Conneely, K. Silander, L. J. Scott, K. L. Mohlke, K. N. Lazaridis, T. T. Valle, J. Tuomilehto, R. N. Bergman, R. M. Watanabe, T. A. Buchanan, F. S. Collins, M. Boehnke

Published in: Diabetologia | Issue 10/2004

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Abstract

Aims/hypothesis

Resistin is a peptide hormone produced by adipocytes that is present at high levels in sera of obese mice and may be involved in glucose homeostasis through regulation of insulin sensitivity. Several studies in humans have found associations between polymorphisms in the resistin gene and obesity, insulin sensitivity and blood pressure. An association between variation in the resistin gene and Type 2 diabetes has been reported in some, but not all studies. The aim of this study was to analyse variants of the resistin gene for association with Type 2 diabetes and related traits in a Finnish sample.

Methods

In 781 cases with Type 2 diabetes, 187 spouse controls and 222 elderly controls of Finnish origin, we genotyped four previously identified non-coding single-nucleotide polymorphisms (SNPs): -420C>G from the promoter region, +156C>T and +298G>A from intron 2, and +1084G>A from the 3′ untranslated region. We then tested whether these SNPs were associated with Type 2 diabetes and related traits.

Results

The SNPs were not significantly associated with Type 2 diabetes. However, SNPs −420C>G, +156C>T and +298G>A and the common haplotype for these three markers were associated with increased values of weight-related traits and diastolic blood pressure in cases, lower weight in elderly control subjects, and lower insulin sensitivity and greater acute insulin response in spouses. Furthermore, the +1084G allele was associated with lower HDL cholesterol in both cases and controls, higher systolic blood pressure and waist circumference in cases, and greater acute insulin response in spouse controls.

Conclusions/interpretation

Our results add to growing evidence that resistin is associated with variation in weight, fat distribution and insulin resistance.
Appendix
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Literature
1.
go back to reference Steppan CM, Bailey ST, Bhat S et al. (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312CrossRefPubMed Steppan CM, Bailey ST, Bhat S et al. (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312CrossRefPubMed
2.
go back to reference Way JM, Gorgun CZ, Tong Q et al. (2001) Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 276:25651–25653CrossRefPubMed Way JM, Gorgun CZ, Tong Q et al. (2001) Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 276:25651–25653CrossRefPubMed
3.
go back to reference Juan CC, Au LC, Fang VS et al. (2001) Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. Biochem Biophys Res Commun 289:1328–1333CrossRefPubMed Juan CC, Au LC, Fang VS et al. (2001) Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. Biochem Biophys Res Commun 289:1328–1333CrossRefPubMed
4.
go back to reference Banerjee RR, Rangwala SM, Shapiro JS et al. (2004) Regulation of fasted blood glucose by resistin. Science 303:1195–1198CrossRefPubMed Banerjee RR, Rangwala SM, Shapiro JS et al. (2004) Regulation of fasted blood glucose by resistin. Science 303:1195–1198CrossRefPubMed
5.
go back to reference Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM (2002) Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res 10:1–5PubMed Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM (2002) Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res 10:1–5PubMed
6.
go back to reference Nagaev I, Smith U (2001) Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 285:561–564CrossRefPubMed Nagaev I, Smith U (2001) Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 285:561–564CrossRefPubMed
7.
go back to reference Savage DB, Sewter CP, Klenk ES et al. (2001) Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 50:2199–2202PubMed Savage DB, Sewter CP, Klenk ES et al. (2001) Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 50:2199–2202PubMed
8.
go back to reference Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R (2001) Tumor necrosis factor alpha is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes. Biochem Biophys Res Commun 288:1027–1031CrossRefPubMed Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R (2001) Tumor necrosis factor alpha is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes. Biochem Biophys Res Commun 288:1027–1031CrossRefPubMed
9.
go back to reference Haugen F, Jorgensen A, Drevon CA, Trayhurn P (2001) Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett 507:105–108CrossRefPubMed Haugen F, Jorgensen A, Drevon CA, Trayhurn P (2001) Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett 507:105–108CrossRefPubMed
10.
go back to reference Kim KH, Lee K, Moon YS, Sul HS (2001) A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276:11252–11256CrossRefPubMed Kim KH, Lee K, Moon YS, Sul HS (2001) A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276:11252–11256CrossRefPubMed
11.
go back to reference Banerjee RR, Lazar MA (2003) Resistin: molecular history and prognosis. J Mol Med 81:218–226PubMed Banerjee RR, Lazar MA (2003) Resistin: molecular history and prognosis. J Mol Med 81:218–226PubMed
12.
go back to reference Smith SR, Bai F, Charbonneau C, Janderova L, Argyropoulos G (2003) A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 52:1611–1618PubMed Smith SR, Bai F, Charbonneau C, Janderova L, Argyropoulos G (2003) A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 52:1611–1618PubMed
13.
go back to reference Engert JC, Vohl MC, Williams SM et al. (2002) 5′ flanking variants of resistin are associated with obesity. Diabetes 51:1629–1634PubMed Engert JC, Vohl MC, Williams SM et al. (2002) 5′ flanking variants of resistin are associated with obesity. Diabetes 51:1629–1634PubMed
14.
go back to reference Wang H, Chu WS, Hemphill C, Elbein SC (2002) Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians. J Clin Endocrinol Metab 87:2520–2524CrossRefPubMed Wang H, Chu WS, Hemphill C, Elbein SC (2002) Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians. J Clin Endocrinol Metab 87:2520–2524CrossRefPubMed
15.
go back to reference Pizzuti A, Argiolas A, Di Paola R et al. (2002) An ATG repeat in the 3′-untranslated region of the human resistin gene is associated with a decreased risk of insulin resistance. J Clin Endocrinol Metab 87:4403–4406CrossRefPubMed Pizzuti A, Argiolas A, Di Paola R et al. (2002) An ATG repeat in the 3′-untranslated region of the human resistin gene is associated with a decreased risk of insulin resistance. J Clin Endocrinol Metab 87:4403–4406CrossRefPubMed
16.
go back to reference Tan MS, Chang SY, Chang DM, Tsai JC, Lee YJ (2003) Association of resistin gene 3′-untranslated region +62G>A polymorphism with type 2 diabetes and hypertension in a Chinese population. J Clin Endocrinol Metab 88:1258–1263CrossRefPubMed Tan MS, Chang SY, Chang DM, Tsai JC, Lee YJ (2003) Association of resistin gene 3′-untranslated region +62G>A polymorphism with type 2 diabetes and hypertension in a Chinese population. J Clin Endocrinol Metab 88:1258–1263CrossRefPubMed
17.
go back to reference Ma X, Warram JH, Trischitta V, Doria A (2002) Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians. J Clin Endocrinol Metab 87:4407–4410CrossRefPubMed Ma X, Warram JH, Trischitta V, Doria A (2002) Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians. J Clin Endocrinol Metab 87:4407–4410CrossRefPubMed
18.
go back to reference Osawa H, Onuma H, Murakami A et al. (2002) Systematic search for single nucleotide polymorphisms in the resistin gene: the absence of evidence for the association of three identified single nucleotide polymorphisms with Japanese type 2 diabetes. Diabetes 51:863–866PubMed Osawa H, Onuma H, Murakami A et al. (2002) Systematic search for single nucleotide polymorphisms in the resistin gene: the absence of evidence for the association of three identified single nucleotide polymorphisms with Japanese type 2 diabetes. Diabetes 51:863–866PubMed
19.
go back to reference Ochi M, Osawa H, Onuma H et al. (2003) The absence of evidence for major effects of the frequent SNP +299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes. Diabetes Res Clin Pract 61:191–198CrossRefPubMed Ochi M, Osawa H, Onuma H et al. (2003) The absence of evidence for major effects of the frequent SNP +299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes. Diabetes Res Clin Pract 61:191–198CrossRefPubMed
20.
go back to reference Sentinelli F, Romeo S, Arca M et al. (2002) Human resistin gene, obesity, and type 2 diabetes: mutation analysis and population study. Diabetes 51:860–862PubMed Sentinelli F, Romeo S, Arca M et al. (2002) Human resistin gene, obesity, and type 2 diabetes: mutation analysis and population study. Diabetes 51:860–862PubMed
21.
go back to reference Cao H, Hegele RA (2001) Single nucleotide polymorphisms of the resistin (RSTN) gene. J Hum Genet 46:553–555CrossRefPubMed Cao H, Hegele RA (2001) Single nucleotide polymorphisms of the resistin (RSTN) gene. J Hum Genet 46:553–555CrossRefPubMed
22.
go back to reference Urbanek M, Du Y, Silander K et al. (2003) Variation in resistin gene promoter not associated with polycystic ovary syndrome. Diabetes 52:214–217PubMed Urbanek M, Du Y, Silander K et al. (2003) Variation in resistin gene promoter not associated with polycystic ovary syndrome. Diabetes 52:214–217PubMed
23.
go back to reference Valle T, Tuomilehto J, Bergman RN et al. (1998) Mapping genes for NIDDM. Design of the Finland-United States Investigation of NIDDM Genetics (FUSION) Study. Diabetes Care 21:949–958PubMed Valle T, Tuomilehto J, Bergman RN et al. (1998) Mapping genes for NIDDM. Design of the Finland-United States Investigation of NIDDM Genetics (FUSION) Study. Diabetes Care 21:949–958PubMed
24.
go back to reference Silander K, Mohlke KL, Scott LJ et al. (2004) Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141–1149PubMed Silander K, Mohlke KL, Scott LJ et al. (2004) Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141–1149PubMed
25.
go back to reference Mohlke KL, Erdos MR, Scott LJ et al. (2002) High-throughput screening for evidence of association by using mass spectrometry genotyping on DNA pools. Proc Natl Acad Sci USA 99:16928–16933CrossRefPubMed Mohlke KL, Erdos MR, Scott LJ et al. (2002) High-throughput screening for evidence of association by using mass spectrometry genotyping on DNA pools. Proc Natl Acad Sci USA 99:16928–16933CrossRefPubMed
26.
go back to reference Dempster AP, Laird NM, Rubin DB (1977) Maximum likelihood estimation from incomplete data via the EM algorithm. J R Stat Soc 39:1–38 Dempster AP, Laird NM, Rubin DB (1977) Maximum likelihood estimation from incomplete data via the EM algorithm. J R Stat Soc 39:1–38
27.
go back to reference Weyer C, Bogardus C, Mott DM, Pratley RE (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794PubMed Weyer C, Bogardus C, Mott DM, Pratley RE (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794PubMed
28.
go back to reference Bergman, RN (1989) Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 38:1512–1527PubMed Bergman, RN (1989) Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 38:1512–1527PubMed
Metadata
Title
Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects
Authors
K. N. Conneely
K. Silander
L. J. Scott
K. L. Mohlke
K. N. Lazaridis
T. T. Valle
J. Tuomilehto
R. N. Bergman
R. M. Watanabe
T. A. Buchanan
F. S. Collins
M. Boehnke
Publication date
01-10-2004
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1537-x

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