Association Analysis of v-AKT Murine Thymoma Viral Oncogene Homolog 1 (AKT1) Polymorphisms and Type 2 Diabetes Mellitus in the Korean Population

• Published in: Genes & genomics Vol. 31; no. 1; pp. 73 - 83
• Main Authors: Jin, H.S. (Kyung Hee University, Seoul, Republic of Korea), Hong, K.W. (Kyung Hee University, Seoul, Republic of Korea), Lim, J.E. (Kyung Hee University, Seoul, Republic of Korea), Lee, G.J. (Kyung Hee University, Seoul, Republic of Korea), Han, J.H. (Kyung Hee University, Seoul, Republic of Korea), Go, M.J. (National Institute of Health, Seoul, Republic of Korea), Lee, J.Y. (National Institute of Health, Seoul, Republic of Korea), Woo, J.T. (Kyung Hee University, Seoul, Republic of Korea), Park, H.K. (Kyung Hee University, Seoul, Republic of Korea), Oh, B.S. (Kyung Hee University, Seoul, Republic of Korea), E-mail: ohbs@khu.ac.kr
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2009; 한국유전학회
• Subjects: AKT1; Animal Genetics and Genomics; Biomedical and Life Sciences; dyslipidemia; HIPERTENSION; Human Genetics; HYPERTENSION; insulin-signaling pathway; Life Sciences; Microbial Genetics and Genomics; Plant Genetics and Genomics; single nucleotide polymorphism; T2DM; 생물학; T2DM; insulin-signaling pathway; AKT1; dyslipidemia; single nucleotide polymorphism; high blood pressure
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/BF03191140

V-AKT murine thymoma viral oncogene homolog 1 (AKT1) is an important downstream target of the insulin-signaling pathway and may be an important regulator of pancreatic beta cell growth. This study investigated the association of the AKT1 gene with susceptibility to type 2 diabetes mellitus and its related traits. By sequencing the AKT1 gene in 24 unrelated individuals, we identified 32 genetic variations including 30 single nucleotide polymorphisms and 2 deletions. For the association analysis, we selected seven single nucleotide polymorphisms (rs10138227, -726G greater than A; rs3730358, +12574C greater than T; rs2494737, +12656T greater than A; rs2498796, +15761T greater than C; rs2498799, +19087A greater than G; rs2494732, +19789G greater than A; rs3803304, +19835G greater than C) based on minor allele frequency (greater than 0.05) and linkage disequilibrium status. The study included 483 type 2 diabetes patients (206 men and 277 women with mean age 64±2.8 years and mean age at onset 56±8.1 years) and 1,138 non-diabetic control subjects (516 men and 622 women with mean age 64±2.9 years). Two single nucleotide polymorphisms (rs2498796, +15761T greater than C and rs2494732, +19789G greater than A) were found to be associated with risk of type 2 diabetes mellitus, and showed an increased risk of type 2 diabetes mellitus in a recessive model (OR = 1.343, 95% CI 1.021-1.765, p = 0.035 and OR = 1.534, 95% CI 1.058-2.225, p = 0.024, respectively). These SNPs were also associated with diabetes-related traits such as levels of fasting blood glucose and hemoglobin Alc. In addition, type 2 diabetes mellitus patients who also have dyslipidemia or high blood pressure showed significant association with single nucleotide polymorphisms in AKT1 when compared with healthy controls. These results indicate that genetic variation in AKT1 influences the development of type 2 diabetes mellitus in the Korean population.