Gastric inhibitory polypeptide receptor: association analyses for obesity of several polymorphisms in large study groups.
BACKGROUND
Gastric inhibitory polypeptide (GIP) is postulated to be involved in type 2 diabetes mellitus and obesity. It exerts its function through its receptor, GIPR. We genotyped three GIPR SNPs (rs8111428, rs2302382 and rs1800437) in German families with at least one obese index patient, two case-control studies and two cross-sectional population-based studies.


METHODS
Genotyping was performed by MALDI-TOF, ARMS-PCR and RFLP. The family-study: 761 German families with at least one extremely obese child or adolescent (n = 1,041) and both parents (n = 1,522). Case-control study: (a) German obese children (n = 333) and (b) obese adults (n = 987) in comparison to 588 adult lean controls. The two cross-sectional population-based studies: KORA (n = 8,269) and SHIP (n = 4,310).


RESULTS
We detected over-transmission of the A-allele of rs2302382 in the German families (pTDT-Test = 0.0089). In the combined case-control sample, we estimated an odd ratio of 1.54 (95%CI 1.09;2.19, pCA-Test = 0.014) for homozygotes of the rs2302382 A-allele compared to individuals with no A-allele. A similar trend was found in KORA where the rs2302382 A-allele led to an increase of 0.12 BMI units (p = 0.136). In SHIP, however, the A-allele of rs2302382 was estimated to contribute an average decrease of 0.27 BMI units (p-value = 0.031).


CONCLUSIONS
Our data suggest a potential relevance of GIPR variants for obesity. However, additional studies are warranted in light of the conflicting results obtained in one of the two population-based studies.
Vogel
Carla I G
CI
Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany. carla.vogel@uni-due.de
Scherag
André
A
Brönner
Günter
G
Nguyen
Thuy T
TT
Wang
Hai-Jun
HJ
Grallert
Harald
H
Bornhorst
Alexa
A
Rosskopf
Dieter
D
Völzke
Henry
H
Reinehr
Thomas
T
Rief
Winfried
W
Illig
Thomas
T
Wichmann
H-Erich
HE
Schäfer
Helmut
H
Hebebrand
Johannes
J
Hinney
Anke
A
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D055815:Young Adult
D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor