|Title:||Genetic variation in the carbonyl reductase 3 gene confers risk of type 2 diabetes and insulin resistance: A potential regulator of adipogenesis||Authors:||YI-CHENG CHANG
|Issue Date:||2012||Publisher:||Springer Verlag||Journal Volume:||90||Journal Issue:||7||Start page/Pages:||847-858||Source:||Journal of Molecular Medicine||Abstract:||
Prostaglandins are potent modulators of insulin sensitivity. We systemically evaluated the association of 61 tag single-nucleotide polymorphisms (SNP) in 14 genes involved in prostaglandin metabolism with type 2 diabetes. Among all genotyped SNPs, rs10483032 in the CBR3 (carbonyl reductase 3) gene, which encodes for an enzyme converting prostaglandin E2 to prostaglandin F2α, was associated with type 2 diabetes in 760 type 2 diabetic cases and 760 controls (stage-1 study) (P02.0×10-4). The association was validated in 1,615 cases and 1,162 controls (stage-2 study) (P00.009). The A allele at rs10483032 was associated with increased risk of type 2 diabetes (odds ratio01.29; 95% confidence interval01.14-1.47; combined P<0.0001). The association was externally validated in the Finland-United States Investigation of NIDDM Genetics (FUSION) study (P03.7×10-4). The risk A allele was associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) in 1,012 non-diabetic controls and 1,138 non-diabetic subjects from the Stanford Asia- Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. CBR3 gene expression in human abdominal adipose tissue was negatively associated with fasting insulin and HOMA-IR. CBR3 gene expression increased during differentiation of 3T3-L1 preadipocytes into adipocytes. Knockdown of CBR3 in 3T3-L1 preadipocytes enhanced adipogenesis and peroxisome proliferator-activator receptor-γ response element reporter activity. Our results indicated that genetic polymorphism in the CBR3 gene conferred risk of type 2 diabetes and insulin resistance in Chinese. The association was probably mediated through modulation of adipogenesis. ? Springer-Verlag 2012.
|ISSN:||0946-2716||DOI:||10.1007/s00109-012-0898-8||SDG/Keyword:||peroxisome proliferator activated receptor gamma; prostaglandin; prostaglandin E2; prostaglandin F2 alpha; adipogenesis; adult; aged; article; CBR3 gene; cell differentiation; cell strain 3T3; controlled study; female; gene; gene expression; gene frequency; genetic association; genetic risk; genetic variability; genotype; human; insulin resistance; insulin sensitivity; major clinical study; male; non insulin dependent diabetes mellitus; prostaglandin metabolism; single nucleotide polymorphism
|Appears in Collections:||醫學系|
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