Context: Ghrelin is known to play a role in glucose metabolism and in -cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes.

Objective: To examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and with its related phenotypes.

Design and Patients: Ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 non-diabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed.

Results: Nine polymorphisms were identified, and four common polymorphisms (g.-1500C>G, g.-1062G>C, g.-994C>T, g.+408C>A [Leu72Met]) were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal non-diabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as, high-density lipoprotein cholesterol, fasting plasma glucose and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum high-density lipoprotein cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests).

Conclusion: The above four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, a common polymorphism g.-1062G>C in the promoter region of ghrelin gene was found to be significantly associated with serum high density lipoprotein cholesterol levels.