Non-replication of an association of CTNNBL1 polymorphisms and obesity in a population of Central European ancestry

<p>Abstract</p> <p>Background</p> <p>A recent genome-wide association (GWA) study of U.S. Caucasians suggested that eight single nucleotide polymorphisms (SNPs) in <it>CTNNBL1 </it>are associated with obesity and increased fat mass. We analysed the respective SNPs in data from our previously published GWA for early onset obesity (case-control design), in GWA data from a population-based cohort of adults, and in an independent family-based obesity study. We investigated whether variants in <it>CTNNBL1 </it>(including rs6013029) and in three other genes (<it>SH3PXD2B</it>, <it>SLIT3 </it>and <it>FLJ42133</it>,) were associated with obesity.</p> <p>Methods</p> <p>The GWA studies were carried out using Affymetrix^®SNP Chips with approximately 500,000 markers each. In the families, SNP rs6013029 was genotyped using the TaqMan^®allelic discrimination assay. The German case-control GWA included 487 extremely obese children and adolescents and 442 healthy lean individuals. The adult GWA included 1,644 individuals from a German population-based study (KORA). The 775 independent German families consisted of extremely obese children and adolescents and their parents.</p> <p>Results</p> <p>We found no evidence for an association of the reported variants in <it>CTNNBL1 </it>with early onset obesity or increased BMI. Further, in our family-based study we found no evidence for over-transmission of the rs6013029 risk-allele T to obese children. Additionally, we found no evidence for an association of <it>SH3PXD2B</it>, <it>SLIT3 and FLJ42133 </it>variants in our two GWA samples.</p> <p>Conclusion</p> <p>We detected no confirmation of the recent association of variants in <it>CTNNBL1 </it>with obesity in a population of Central European ancestry.</p

Gastric inhibitory polypeptide receptor: association analyses for obesity of several polymorphisms in large study groups

<p>Abstract</p> <p>Background</p> <p>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 <it>GIPR </it>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>We detected over-transmission of the A-allele of rs2302382 in the German families (p_TDT-Test= 0.0089). In the combined case-control sample, we estimated an odd ratio of 1.54 (95%CI 1.09;2.19, p_CA-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).</p> <p>Conclusion</p> <p>Our data suggest a potential relevance of <it>GIPR </it>variants for obesity. However, additional studies are warranted in light of the conflicting results obtained in one of the two population-based studies.</p

Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

<p>Abstract</p> <p>Background</p> <p>The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether <it>FAAH </it>alleles are associated with early and late onset obesity.</p> <p>Methods</p> <p>We initially assessed association of five single nucleotide polymorphisms (SNPs) in <it>FAAH </it>with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the <it>FAAH </it>coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity.</p> <p>Results</p> <p>The trio analysis revealed some evidence for an association of three SNPs in <it>FAAH </it>(rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in <it>FAAH </it>(rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05).</p> <p>Conclusions</p> <p>As we observed some evidence for an association of the <it>FAAH </it>variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the <it>FAAH </it>variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.</p