Identification of Genetic Variations in CBL, SORBS1, CRK, and RHOQ, Key Modulators in the CAP/TC10 Pathway of Insulin Signal Transduction, and Their Association with Type 2 Diabetes Mellitus in the Korean Population

• Published in: Genomics & informatics Vol. 7; no. 2; pp. 53 - 56
• Main Authors: Hong, Kyung-Won, Jin, Hyun-Seok, Lim, Ji-Eun, Go, Min-Jin, Lee, Jong-Young, Hwang, Sue-Yun, Park, Hun-Kuk, Oh, Berm-Seok
• Format: Journal Article
• Language: Korean
• Published: 2009
• Subjects: insulin; SNP; Glut 4; type 2 diabetes mellitus; CAP/TC10
• ISSN: 1598-866X; 2234-0742

Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.