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). Conclusion: 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.