Premium
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
Author(s) -
Lindner Inka,
Helwig Ulf,
Rubin Diana,
Li Yun,
Fisher Eva,
Boeing Heiner,
Möhlig Matthias,
Spranger Joachim,
Pfeiffer Andreas,
Hampe Jochen,
Schreiber Stefan,
Döring Frank,
Schrezenmeir Jürgen
Publication year - 2005
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200500087
Subject(s) - type 2 diabetes , genotype , medicine , european prospective investigation into cancer and nutrition , type 2 diabetes mellitus , body mass index , odds ratio , colipase , endocrinology , diabetes mellitus , population , biology , genetics , gene , lipase , triacylglycerol lipase , enzyme , biochemistry , environmental health
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.