Candidate gene association study of type 2 diabetes in a nested case-control study of the EPIC-Potsdam cohort - role of fat assimilation.
To search for common variants etiological for type 2 diabetes, we screened 15 genes involved in fat assimilation for sequence variants. Approximately 55 kb in promoter and coding regions, and intron/splice sites were sequenced by cycle sequencing. In the set of 15 genes, 71 single nucleotide polymorphisms (SNPs) were detected. 33 SNPs were presumed to be functionally significant and were genotyped in 192 incident type 2 diabetes subjects and 384 matched controls from the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. A total of 27 SNPs out of 15 genes showed no statistical association with type 2 diabetes in our study. Six SNPs demonstrated nominal association with type 2 diabetes, with the most significant marker (FABP6 Thr79Met) having an adjusted odds ratio of 0.45 (95% CI 0.22-0.92) in homozygous Met allele carriers. Evidence for an association with disease status was also found for a novel Arg109Cys (g.2129C > T) variant of colipase, 5'UTR (rs2084202) and Met71Val (rs8192506) variants of diazepam-binding inhibitor, Arg298His (rs13283456) of PTGES2, and a novel promoter variant (g.-1324G > A) of SLC27A5. The results presented here provide preliminary evidence for the association of common variants in genes involved in fat assimilation with the genetic susceptibility of type 2 diabetes. However, they definitely need further verification.
Fisher
Eva
E
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. fisher@dife.de
Nitz
Inke
I
Lindner
Inka
I
Rubin
Diana
D
Boeing
Heiner
H
Möhlig
Matthias
M
Hampe
Jochen
J
Schreiber
Stefan
S
Schrezenmeir
Jürgen
J
Döring
Frank
F
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003089:Colipases / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D050612:Fatty Acid Transport Proteins / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005768:Gastrointestinal Hormones; D020022:Genetic Predisposition to Disease; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071876:Prostaglandin-E Synthases
D003089:Colipases; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005768:Gastrointestinal Hormones; C484819:SLC27A5 protein, human; C057275:fatty acid-binding protein 6; D019746:Intramolecular Oxidoreductases; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases