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Abstract 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.

Background: Both reduced postsynaptic dopamine D2 receptor function and the character variable self-directedness (SDD) are related to the level of alcohol consumption. We examined for interactions between DRD2 exon 8(rs6276), a polymorphism which has been associated with various alcohol-related phenotypes, SDD and alcohol consumption. Methods:A total of 144 male and 186 female probands with alcohol dependence or abuse diagnoses and without were included in the study. All subjects were assessed with the alcohol section of the Semi-Structured Assessment for the Genetics of Alcoholism and the Temperament and Character Inventory. Results: Male probands with A/A genotype reported significantly higher alcohol consumption in a typical week (ANOVA; p = 0.024); those with A/A genotype and low SDD showed particularly high consumption levels (interaction DRD2 × SDD: p = 0.019). Alcohol dependence/abuse (DSM-IV) but not nicotine dependence was also relevant for higher alcohol consumption (trend: p = 0.052). In the female group, only alcohol disorders predicted alcohol consumption. Conclusions:Our findings support a role for a gene-personality interaction of DRD2 exon 8 × SDD in alcohol consumption in males. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hypercarbic respiratory drive is mainly determined by PCO2 and pH with activity of the intracellular Na+/H+ exchanger (NHE) playing an important role in maintaining intracellular pH and respiratory drive. Because NHE activity varies with genetically different G-protein β3 subunits (GNB3) (C/T polymorphism at nucleotide position 825) different genotypes might alter respiratory regulation. To test the hypothesis that short-term ventilatory responses vary with different GNB3 healthy volunteers with different genotypes (CC, TC, TT) were exposed to either hyperoxic hypercarbia (n=33) or to isocapnic hypoxia (n=31), respectively. There was no difference between CC, TC, and TT genotypes in hypercarbic and hypoxic respiratory drive when assessed as the ratio of minute ventilation over endexpiratory PCO2 changes (ΔVE/ΔPETCO2), maximal tolerable PETCO2, and ratio of changes in ventilation over arterial haemoglobin desaturation (ΔVE/ΔSO2), respectively. Thus, short-term hypercarbic and hypoxic ventilatory drive do not differ between individuals with genotypes encoding different GNB3. Whilst respiratory control may still be influenced by G-protein aberration, other mechanisms seem to have a more important role in controlling ventilation. [ABSTRACT FROM AUTHOR]