title: Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.
abstract: OBJECTIVE
  Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs) in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans.
  
  
  METHODS
  We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707). The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR) imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps.
  
  
  RESULTS
  After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels.
  
  
  CONCLUSIONS
  In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Stefan Z
authors.initials: SZ
authors.lastname: Lutz
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Franck
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Böhm
authors.affiliation: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany; Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.affiliation: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany; Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.affiliation: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Nutritional and Preventive Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
mesh_terms: D050154:Adiposity / Q000235:genetics; D000328:Adult; D002885:Chromosomes, Human, Pair 16; D016207:Cytokines / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
chemical_list: D016207:Cytokines; D007328:Insulin; C092073:cardiotrophin 1