Baessler, Andrea and Hasinoff, Michael J. and Fischer, Marcus and Reinhard, Wibke and Sonnenberg, Gabriele E. and Olivier, Michael and Erdmann, Jeanette and Schunkert, Heribert and Doering, Angela and Jacob, Howard J. and Comuzzie, Anthony G. and Kissebah, Ahmed H. and Kwitek, Anne E. (2005) Genetic linkage and association of the growth hormone secretagogue receptor (Ghrelin receptor) gene in human obesity. DIABETES, 54 (1). pp. 259-267. ISSN 0012-1797, 1939-327X
Full text not available from this repository. (Request a copy)Abstract
The growth hormone secretagogue receptor (GHSR) (ghrelin receptor) plays an important role in the regulation of food intake and energy homeostasis. The GHSR gene lies on human chromosome 3q26 within a quantitative trait locus strongly linked to multiple phenotypes related to obesity and the metabolic syndrome. Because the biological function and location of the GHSR gene make it an excellent candidate gene, we tested the relation between common single nucleotide polymorphisms (SNPs) in the GHSR gene and human obesity. We performed a comprehensive analysis of SNPs, linkage disequilibrium (LD), and haplotype structure across the entire GHSR gene region (99.3 kb) in 178 pedigrees with multiple obese members (DNA of 1,095 Caucasians) and in an independent sample of the general population (MONICA Augsburg left ventricular hypertrophy substudy; DNA of 1,418 Caucasians). The LD analysis revealed a disequilibrium block consisting of five SNPs, consistent in both study cohorts. We found linkage among all five SNPs, their haplotypes, and BMI. Further, we found suggestive evidence for transmission disequilibrium for the minor SNP alleles (P < 0.05) and the two most common haplotypes with the obesity affection status ("susceptible" P = 0.025, "nonsusceptible" P = 0.045) in the family cohort using the familybased association test program. Replication of these findings in the general population resulted in stronger evidence for an association of the SNPs (best P = 0.00001) and haplotypes with the disease ("susceptible" P = 0.002, "nonsusceptible" P = 0.002). To our knowledge, these data are the first to demonstrate linkage and association of SNPs and haplotypes within the GHSR gene region and human obesity. This linkage, together with significant transmission disequilibrium in families and replication of this association in an independent population, provides evidence that common SNPs and haplotypes within the GHSR region are involved in the pathogenesis of human obesity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SINGLE-NUCLEOTIDE POLYMORPHISMS; FAMILY-BASED TESTS; BODY-MASS INDEX; QUANTITATIVE TRAITS; DISEQUILIBRIUM; IDENTIFICATION; WEIGHT; GENOME; SUSCEPTIBILITY; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2021 05:29 |
| Last Modified: | 02 Jun 2021 05:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36675 |
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