Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg.

OBJECTIVE Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the development of several components of metabolic syndrome (MetS). The present study investigated the association of nine MCP-1 single nucleotide polymorphisms (SNPs) with MetS, type 2 diabetes mellitus and metabolic risk factors. SUBJECTS AND METHODS The population-based study sample comprised 1630 subjects aged 55-74 years from KORA S4 (Cooperative Health Research in the Region of Augsburg Survey 4). Genotyping was carried out by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis of allele-dependent primer extension products. RESULTS The MCP-1 SNP c.-3813C>T exhibited trends for differences between the genotype groups in triglycerides, 2-h glucose and uric acid (P = 0.0084, 0.014, 0.027). Other trends were observed for c.-928G>C associated with height and fasting glucose (P = 0.0024, 0.033), for c.105T>C with height and leukocytes (P = 0.0095, 0.047), for c.*65C>T and c.*3879C>T with MCP-1 levels (both P = 0.012) and for c.-2138A>T with interleukin-6 levels. After correction for multiple testing, none of the analysed SNPs, except c.-928G>C in men showed a significant association with MetS, T2DM or other analysed parameters. Haplotype MCP-1*1 and c.-928G>C in men (P = 0.0002, 0.0004) were significantly associated with an increase in height. CONCLUSIONS This is the first study to investigate the associations of MCP-1 SNPs with MetS. We found trends for several components of MetS. These parameters were hyperlipidaemia, fasting and 2-h glucose, and uric acid. A new finding is that MCP-1*1 haplotype is associated with height. Further investigation in larger populations is needed to clarify the involvement of MCP-1 in MetS.

[1]  T. Illig,et al.  Significant association of a M129V independent polymorphism in the 5′ UTR of the PRNP gene with sporadic Creutzfeldt-Jakob disease in a large German case-control study , 2006, Journal of Medical Genetics.

[2]  Thomas Meitinger,et al.  SNP-Based Analysis of Genetic Substructure in the German Population , 2006, Human Heredity.

[3]  W. Rathmann,et al.  IL-6 promoter polymorphisms and quantitative traits related to the metabolic syndrome in KORA S4 , 2006, Experimental Gerontology.

[4]  C. Ting,et al.  The presence of metabolic syndrome is independently associated with elevated serum CD40 ligand and disease severity in patients with symptomatic coronary artery disease. , 2006, Metabolism: clinical and experimental.

[5]  Yoshiya Tanaka,et al.  Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus. , 2006, Biochemical and biophysical research communications.

[6]  R. Koppensteiner,et al.  Effect of Massive Weight Loss induced by Bariatric Surgery on Serum Levels of Interleukin-18 and Monocyte-Chemoattractant-Protein-1 in Morbid Obesity , 2006, Obesity surgery.

[7]  R. Kitazawa,et al.  MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. , 2006, The Journal of clinical investigation.

[8]  B. Coll,et al.  The influence of HIV infection on the correlation between plasma concentrations of monocyte chemoattractant protein-1 and carotid atherosclerosis. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[9]  J. Shaw,et al.  Metabolic syndrome—a new world‐wide definition. A Consensus Statement from the International Diabetes Federation , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[10]  C. Meisinger,et al.  Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002 , 2006, Diabetologia.

[11]  P. Raggi,et al.  Increased concentration of proatherogenic inflammatory cytokines in systemic lupus erythematosus: relationship to cardiovascular risk factors. , 2006, The Journal of rheumatology.

[12]  Y. Aso,et al.  Association between circulating monocyte chemoattractant protein-1 and urinary albumin excretion in nonobese Type 2 diabetic patients. , 2006, Journal of diabetes and its complications.

[13]  Takahiko Nakagawa,et al.  A causal role for uric acid in fructose-induced metabolic syndrome. , 2006, American journal of physiology. Renal physiology.

[14]  R. Holle,et al.  Systemic monocyte chemoattractant protein-1 concentrations are independent of type 2 diabetes or parameters of obesity: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). , 2006, European journal of endocrinology.

[15]  J. Drabek,et al.  The MCP‐1 −2518 (A to G) single nucleotide polymorphism is not associated with myocardial infarction in the Czech population , 2005, International journal of immunogenetics.

[16]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.

[17]  U. Müller-Ladner,et al.  Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein‐1 that are not influenced by the –2518 A→G promoter polymorphism , 2005, Diabetes, obesity & metabolism.

[18]  Richard Kahn,et al.  The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. , 2005, Diabetes care.

[19]  J. Hirschhorn,et al.  CCL2 Polymorphisms Are Associated With Serum Monocyte Chemoattractant Protein-1 Levels and Myocardial Infarction in the Framingham Heart Study , 2005, Circulation.

[20]  R. Sacco,et al.  Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study , 2005, Diabetologia.

[21]  R Holle,et al.  KORA - A Research Platform for Population Based Health Research , 2005, Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)).

[22]  C. Gieger,et al.  KORA-gen - Resource for Population Genetics, Controls and a Broad Spectrum of Disease Phenotypes , 2005 .

[23]  C. Ballantyne,et al.  Multiplexed analysis of biomarkers related to obesity and the metabolic syndrome in human plasma, using the Luminex-100 system. , 2005, Clinical chemistry.

[24]  N. Morrison,et al.  MCP-1 Is Induced by Receptor Activator of Nuclear Factor-κB Ligand, Promotes Human Osteoclast Fusion, and Rescues Granulocyte Macrophage Colony-stimulating Factor Suppression of Osteoclast Formation* , 2005, Journal of Biological Chemistry.

[25]  S. B. Pedersen,et al.  Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. , 2005, The Journal of clinical endocrinology and metabolism.

[26]  J. Pascasio,et al.  Lack of association of recipient MCP-1 gene promoter polymorphism with acute graft rejection after orthotopic liver transplantation. , 2005, Transplantation proceedings.

[27]  W. Harris,et al.  Metabolic syndrome-mediated inflammation following elective percutaneous coronary intervention , 2005, Diabetes & vascular disease research.

[28]  A. Khera,et al.  Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. , 2004, Journal of the American College of Cardiology.

[29]  W. März,et al.  Association between the A–2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus , 2004, Diabetologia.

[30]  D. Nyholt.  A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. , 2004, American journal of human genetics.

[31]  J. Lukl,et al.  Monocyte chemoattractant protein-1 in patients with peripheral arterial disease. , 2004, Mediators of inflammation.

[32]  K. Kohara,et al.  Polymorphism of the monocyte chemoattractant protein (MCP-1) gene is associated with the plasma level of MCP-1 but not with carotid intima-media thickness. , 2003, Hypertension research : official journal of the Japanese Society of Hypertension.

[33]  D. Loskutoff,et al.  Monocyte chemoattractant protein 1 in obesity and insulin resistance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. Oberbauer,et al.  Alendronate affects long bone length and growth plate morphology in the oim mouse model for Osteogenesis Imperfecta. , 2003, Bone.

[35]  H. Löwel,et al.  High prevalence of undiagnosed diabetes mellitus in Southern Germany: Target populations for efficient screening. The KORA survey 2000 , 2003, Diabetologia.

[36]  W. Kübler,et al.  Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-kappaB and activator protein-1. , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[37]  W. Rathmann,et al.  Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-α or its receptors , 2002, Diabetologia.

[38]  D. Schaid,et al.  Score tests for association between traits and haplotypes when linkage phase is ambiguous. , 2002, American journal of human genetics.

[39]  A. Falus,et al.  Lack of association between atopic eczema/dermatitis syndrome and polymorphisms in the promoter region of RANTES and regulatory region of MCP‐1 , 2002, Allergy.

[40]  L. Groop,et al.  The dysmetabolic syndrome , 2001, Journal of internal medicine.

[41]  M. Baggiolini.  Chemokines in pathology and medicine , 2001, Journal of internal medicine.

[42]  H. Arai,et al.  Distinct Signaling Pathways for MCP-1-dependent Integrin Activation and Chemotaxis* , 2001, The Journal of Biological Chemistry.

[43]  A. Strosberg,et al.  Chemokines control fat accumulation and leptin secretion by cultured human adipocytes , 2001, Molecular and Cellular Endocrinology.

[44]  B. Okopień,et al.  Levels of sICAM-1, sVCAM-1 and MCP-1 in patients with hyperlipoproteinemia IIa and -IIb. , 2001, International journal of clinical pharmacology and therapeutics.

[45]  B. Rovin,et al.  A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. , 1999, Biochemical and biophysical research communications.

[46]  F. Luscinskas,et al.  MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions , 1999, Nature.

[47]  B. Rollins,et al.  MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. , 1999, The Journal of clinical investigation.

[48]  G. Randolph,et al.  A soluble gradient of endogenous monocyte chemoattractant protein-1 promotes the transendothelial migration of monocytes in vitro. , 1995, Journal of immunology.

[49]  C. Y. Wang,et al.  Monocyte chemoattractant protein-1 expression and monocyte recruitment in osseous inflammation in the mouse. , 1995, Endocrinology.

[50]  S. Coughlin,et al.  Monocyte chemoattractant protein-1 in human atheromatous plaques. , 1991, The Journal of clinical investigation.

[51]  W. Fiers,et al.  Search for mediators of the lipogenic effects of tumor necrosis factor: potential role for interleukin 6. , 1990, Cancer research.

[52]  F. López‐Soriano,et al.  Interleukin-1 and lipid metabolism in the rat. , 1989, The Biochemical journal.

[53]  J. Hirschhorn,et al.  CCL 2 Polymorphisms Are Associated With Serum Monocyte Chemoattractant Protein-1 Levels and Myocardial Infarction in the Framingham Heart Study , 2005 .

[54]  B. Richelsen,et al.  Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects , 2005, International Journal of Obesity.

[55]  H. Minuk,et al.  Metabolic syndrome. , 2005, Journal of insurance medicine.