Faculty Collaboration Database

Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Diabetes 2005 Jan;54(1):259-67

Date

12/24/2004

Pubmed ID

15616037

Pubmed Central ID

PMC2793077

DOI

10.2337/diabetes.54.1.259

Scopus ID

2-s2.0-19944427023 (requires institutional sign-in at Scopus site)   81 Citations

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 family-based 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.

Author List

Baessler A, Hasinoff MJ, Fischer M, Reinhard W, Sonnenberg GE, Olivier M, Erdmann J, Schunkert H, Doering A, Jacob HJ, Comuzzie AG, Kissebah AH, Kwitek AE

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Body Mass Index
Body Size
Chromosome Mapping
Energy Intake
Energy Metabolism
Female
Gene Frequency
Humans
Linkage Disequilibrium
Male
Middle Aged
Obesity
Polymorphism, Single Nucleotide
Receptors, G-Protein-Coupled
Receptors, Ghrelin