Polymorphisms in the Ghrelin Gene Are Associated with Serum High-Density Lipoprotein Cholesterol Level and not with Type 2 Diabetes Mellitus in Koreans

• Published in: The journal of clinical endocrinology and metabolism Vol. 91; no. 11; pp. 4657 - 4663
• Main Authors: Choi, Hyung Jin, Cho, Young Min, Moon, Min Kyong, Choi, Hye Hun, Shin, Hyoung Doo, Jang, Hak Chul, Kim, Seong Yeon, Lee, Hong Kyu, Park, Kyong Soo
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.11.2006; Copyright by The Endocrine Society
• Subjects: Aged; Biological and medical sciences; Cholesterol, HDL - blood; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA-Binding Proteins - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Genetic Linkage; Ghrelin; Humans; Korea - epidemiology; Male; Medical sciences; Middle Aged; Peptide Hormones - genetics; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic; Sequence Analysis, DNA; Transcription Factors - metabolism; Transcriptional Activation; Vertebrates: endocrinology; Asia; Korea; Endocrinopathy; Type 2 diabetes; Genetic variability; Cholesterol HDL; Ghrelin; Metabolic diseases; Genotype; Serum; Endocrinology; Polymorphism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-2549

Context: Ghrelin is known to play a role in glucose metabolism and in β-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. Objective: The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. Design and Patients: The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic 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 nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.−1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). Conclusion: The aforementioned 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, the common polymorphism g.−1062G>C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.