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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Estrogen receptor alpha gene variants associate with type 2 diabetes and fasting plasma glucose.

OBJECTIVE: Estrogen receptor 1 (ESR1) mediates effects of estrogens on glucose homeostasis. Polymorphisms in intron 1, 2, and 4 of the ESR1 gene have been found to be associated with type 2 diabetes (T2D) in Hungarian, Chinese, and African-American and European-American cohorts. The aim of this study was to investigate the association between ESR1 polymorphisms and T2D as well as quantitative phenotypes related to glucose homeostasis in French and Swedish Caucasians. METHODS: The French cohort included 941 normoglycemic controls and 988 T2D patients. The Swedish cohort consisted of 1045 controls with normal glucose tolerance, 324 participants with impaired glucose tolerance, and 276 T2D patients. A total of 20 single nucleotide polymorphisms (SNPs) distributed across the ESR1 gene were genotyped. RESULTS: SNPs in introns 3 and 4 of the ESR1 gene associated significantly with T2D in the French cohort (rs3020314, rs985694, P = 0.0009-0.001) and with fasting plasma glucose in Swedish men (rs9397456, rs3020314 rs3020317, P = 0.0002-0.0022) after Bonferroni correction for the analysis of 20 SNPs. In addition, nominal association of ESR1 rs1884051 (P=0.011) with T2D in the French cohort replicates a previously observed association in Finns (empirical P=0.024) ( CONCLUSION: This study provides further evidence that ESR1 genetic polymorphisms are associated with T2D and with fasting plasma glucose. No current evidence that the investigated SNPs are functional is present, thus, we suggest that the association between T2D and ESR1 variants may be because of other unidentified ESR1 polymorphisms that regulate glucose homeostasis.[1]


  1. Estrogen receptor alpha gene variants associate with type 2 diabetes and fasting plasma glucose. Dahlman, I., Vaxillaire, M., Nilsson, M., Lecoeur, C., Gu, H.F., Cavalcanti-Proença, C., Efendic, S., Ostenson, C.G., Brismar, K., Charpentier, G., Gustafsson, J.A., Froguel, P., Dahlman-Wright, K., Steffensen, K.R. Pharmacogenet. Genomics (2008) [Pubmed]
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