title: RAPGEF1 gene variants associated with type 2 diabetes in the Korean population.
abstract: Under the activation of insulin receptors, glucose transporter 4 (Glut4) translocation is regulated by two signal transduction pathways. These pathways are the PI 3-kinase-dependent pathway and the CAP/TC10 pathway. The adaptor protein Rap guanine exchange factor 1 (RAPGEF1) also known as C3G is a component of the CAP/TC10 pathway. Defects in the RAPGEF1 protein may contribute to insulin resistance and type 2 diabetes. Recently, the RAPGEF1 gene was suggested to be involved in the development of type 2 diabetes by FUSION study. To investigate this association in the Korean population, we sequenced the RAPGEF1 gene in 24 unrelated individuals and identified 39 sequence variants. Eleven single nucleotide polymorphisms (SNPs) were selected and genotyped in 1122 Korean patients with type 2 diabetes. There were 1138 non-diabetic controls. Using a logistic regression analysis, a significant association was found between SNP rs11243444 in the RAPGEF1 gene and type 2 diabetes [OR=0.490 (95% CI 0.296-0.813), p=0.006] in the recessive model, leading the protective effect of the GG genotype on the disease development. The present study examines genetic polymorphisms in the RAPGEF1 gene, and the positive association between one polymorphism and type 2 diabetes in the Korean population.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Kyung Hee University, 1 Hoeki-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Hong
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Jin
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lim
authors.forename: Ha-Jung
authors.initials: HJ
authors.lastname: Ryu
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Go
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jeong-Taek
authors.initials: JT
authors.lastname: Woo
authors.forename: Hun Kuk
authors.initials: HK
authors.lastname: Park
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
mesh_terms: D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D007723:Korea; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D009419:Nerve Tissue Proteins; C403525:RAPGEF2 protein, human