Association of variants in gastric inhibitory polypeptide receptor gene with impaired glucose homeostasis in obese children and adolescents from Berlin.
OBJECTIVE
In the past 20 years, obesity has become a major health problem due to associated diseases like type 2 diabetes mellitus. The gastric inhibitory polypeptide receptor (GIPR) modulates body weight and glucose homeostasis and, therefore, represents an interesting candidate gene for obesity and the comorbidity impaired glucose homeostasis. Recently, a GIPR variation was found to be associated with impaired insulin response in humans. In this study, we screened the GIPR gene for mutations and examined the association between three single-nucleotide polymorphisms (SNPs; rs8111428, rs2302382, rs1800437) and childhood obesity, as well as impaired glucose homeostasis.


METHODS
The coding region of the GIPR was screened for mutations by direct sequencing. We genotyped three known SNPs in 2280 healthy normal weight (1696) and obese (584) children and adolescents. Genotyping was performed using the SNaPshot protocol, the iplex, and matrix-assisted laser desorption ionization time-of-flight spectrometry technique. Obesity was defined by a body mass index SDS above 2; homeostatic model assessment was calculated.


RESULTS
No evidence for an association was found between the SNPs and the obesity phenotype. Significant association was found between the minor allele C of the SNP rs1800437 and elevated homeostasis model of insulin resistance values (P=0.001). No further sequence variations in the GIPR were found to be associated with childhood obesity.


CONCLUSIONS
Variations of the GIPR sequence are not associated with childhood obesity. This study points to a potential role for rs1800437 in glucose homeostasis. Further studies are necessary to confirm these results.
Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Jeannine
J
Sauber
Jessica
J
Grothe
Maria
M
Behm
André
A
Scherag
Harald
H
Grallert
Thomas
T
Illig
Anke
A
Hinney
Johannes
J
Hebebrand
Susanna
S
Wiegand
Annette
A
Grüters
Heiko
H
Krude
Heike
H
Biebermann
D000293:Adolescent; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics*; D001835:Body Weight / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D005858:Germany; D018149:Glucose Intolerance / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
D001786:Blood Glucose; D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor