Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome.
Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin release via interaction with its pancreatic receptor (GIP receptor (GIPR)). GIP also acts as vasoactive protein. To investigate whether variations in GIP and GIPR genes are associated with risk factors of the metabolic syndrome we sequenced gene regions and identified two coding SNPs (GIP Ser103Gly, GIPR Glu354Gln) and one splice site SNP (GIP rs2291726) in 47 subjects. Interestingly, in silico analyses revealed that splice site SNP rs2291726 results in a truncated protein and classified GIPR variant Glu354Gln as a functional amino acid change. Association analyses were performed in a case-cohort study of incident cardiovascular disease (CVD) nested in the EPIC-Potsdam cohort. No significant associations between incident CVD and GIP Ser103Gly and rs2291726 were found. For GIPR Glu354Gln, we obtained a nominal association of heterozygous minor allele carrier with CVD in a codominant model adjusted for BMI, sex, and age (OR: 0.67, CI: 0.50-0.91, p = 0.01) or additional covariates of CVD (OR: 0.72, CI: 0.52-0.97, p = 0.03). In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD.
Nitz
Inke
I
Department of Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts University, Kiel, Germany.
Fisher
Eva
E
Weikert
Cornelia
C
Burwinkel
Barbara
B
Li
Yun
Y
Möhlig
Matthias
M
Boeing
Heiner
H
Schreiber
Stefan
S
Schrezenmeir
Jürgen
J
Döring
Frank
F
D000595:Amino Acid Sequence; D002318:Cardiovascular Diseases / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors / Q000737:chemistry; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry / Q000235:genetics*
D011498:Protein Precursors; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor