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Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population

Cited 31 time in Web of Science Cited 32 time in Scopus
Authors
Kim, J H; Shin, H D; Park, B L; Cho, Y M; Kim, S Y; Lee, H K; Park, K S
Issue Date
2005-06-07
Publisher
Springer Verlag
Citation
Diabetologia. 2005 Jul;48(7):1323-30. Epub 2005 Jun 4.
Keywords
Age of OnsetAgedChromosome MappingChromosomes, Human, Pair 4Diabetes Mellitus, Type 2/*geneticsGenotypeHeat-Shock Proteins/*geneticsHumansKoreaLinkage DisequilibriumMiddle Aged*Polymorphism, Genetic*Promoter Regions, GeneticTranscription Factors/*genetics
Abstract
AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) is a transcriptional coactivator implicated in insulin release by beta cells and in insulin resistance. Therefore, genetic variation of PPARGC1A could be implicated in the onset of type 2 diabetes. In this study, we examined whether the PPARGC1A gene locus is associated with type 2 diabetes mellitus. We also investigated its association with clinical and metabolic parameters in healthy and diabetic subjects. METHODS: After sequencing exons and their boundaries of the PPARGC1A gene, including the promoter region ( approximately 1.5 kb), we genotyped eight common single nucleotide polymorphisms (SNPs) in an association study comprising 762 unrelated patients with type 2 diabetes and 303 non-diabetic control patients. We divided the patients with type 2 diabetes into quartiles or three groups according to age at diagnosis of type 2 diabetes (early-onset: <40 years of age, average-onset: 40< or = <60 years, and late-onset: > or =60 years). RESULTS: There was no strong association between SNPs or haplotypes of PPARGC1A and type 2 diabetes. However, the SNPs of g.-1789G>A and g.-1437C>T were associated with the age at diagnosis of type 2 diabetes (p=0.042 and p=0.032, respectively). In addition, the promoter SNPs of g.-1789G>A and g.-1437C>T and the haplotypes ht2 (-1789A and -1437T) were significantly associated with early-onset type 2 diabetes (p=0.002, p=0.001 and p=0.001, respectively). CONCLUSIONS/INTERPRETATION: Our results suggest that PPARGC1A promoter polymorphisms are associated with age at diagnosis of type 2 diabetes and early-onset type 2 diabetes in the Korean population.
ISSN
0012-186X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15937669

http://hdl.handle.net/10371/27574
DOI
https://doi.org/10.1007/s00125-005-1793-4
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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