title: Putative association between a new polymorphism in exon 3 (Arg109Cys) of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations.
abstract: The protein encoded by the pancreatic colipase (CLPS) gene is an essential cofactor needed by pancreatic triglyceride lipase (PNLIP) for efficient dietary lipid hydrolysis. Since the inhibition of lipase activity was shown to reduce the incidence of type 2 diabetes mellitus, we tested the hypothesis that genetic variations in the CLPS and PNLIP genes are associated with type 2 diabetes; 47 unrelated subjects were screened for polymorphisms of the CLPS and PNLIP genes. A nested-case control study of 192 incident type 2 diabetes subjects and 384 sex- and age-matched controls taken from the European Prospective Investigation into Cancer and Nutrition Potsdam Cohort (EPIC) was employed for association studies. The Metabolic Intervention Cohort Kiel (MICK) consisting of 716 males was used for verification. A novel putative functional polymorphism (Arg109Cys) was identified in the CLPS gene. The frequencies of the Arg/Cys genotype were 2.6% in EPIC and 2.2% in MICK study subjects. No homozygotes for the Cys/Cys genotype were found in either study population. Logistic regression analysis showed a statistically significant association of the Arg/Cys genotype with an increased risk of type 2 diabetes. The odds ratios estimated by the model were 3.75 (95%CI = 1.13-12.49, p = 0.03) in EPIC and 4.86 (95%CI = 1.13-20.95, p = 0.03) in MICK. No comparable associations were found with other traits of the insulin-resistance syndrome (e. g.; body mass index, waist to hip ratio). In conclusion, we obtained evidence in two German Caucasian study populations that the variant of the rare CLPS Arg109Cys polymorphism might contribute to increased susceptibility of type 2 diabetes.
authors.affiliation: Institute for Physiology and Biochemistry of Nutrition, Federal Research Center for Nutrition and Food, Hermann-Weigmann-Strasse 1, 24103 Kiel, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Lindner
authors.forename: Ulf
authors.initials: U
authors.lastname: Helwig
authors.forename: Diana
authors.initials: D
authors.lastname: Rubin
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Matthias
authors.initials: M
authors.lastname: Möhlig
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfeiffer
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schrezenmeir
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003089:Colipases / Q000235:genetics*; D004247:DNA / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008049:Lipase / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: D003089:Colipases; D004247:DNA; D008049:Lipase