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Association of Atrogin‐1 genotypes with Metabolic Syndrome Risk Factors in Caucasian Females
Author(s) -
Suer Funda Elif Orkunoglu,
Devaney Joseph M,
GordishDressman Heather,
Hoffman Eric P
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb119
Subject(s) - medicine , endocrinology , single nucleotide polymorphism , insulin resistance , diabetes mellitus , genotype , insulin , population , snp , biology , genetics , gene , environmental health
PURPOSE: Atrogin‐1 is a regulator of the ATP‐ubiquitin‐proteasome system ‐dependent muscle proteolysis (UB’P), which is altered in diabetes and other catabolic states. The objective of this study was to examine the effects of single nucleotide polymorphisms (SNPs) in the human Atrogin‐1 gene on metabolic syndrome risk factors in a young, pre‐diabetic population. METHODS: We analyzed three Atrogin‐1 SNPs (rs4871385, rs6690663, rs3739287) in a Caucasian subpopulation (446 females; 312 males; age 24 ± 8 y) in a 12 wk supervised resistance training intervention. Fasting blood draws, ht, wt and resting blood pressure were collected from subjects prior to onset of an exercise training period. Genotyping was done using a TaqMan assay. Serum samples were assessed for glucose, insulin, triglycerides and HDL levels. Associations between the SNP and each phenotype were testing using ANCOVA with Sidak post‐hoc tests. Each model included baseline body weight and age as covariates. RESULTS: In females, the G202A SNP (rs3739287) was found significantly affect homeostasis model assessment (HOMA) (GG: 1.04 ± 0.08 vs. AG/AA 1.71 ± 0.18; p = 0.0006), fasting glucose (GG: 85.08 ± 0.41 vs. AG/AA 87.09 ± 0.88; p = 0.0383), insulin (GG: 4.92 ± 0.28 vs. AG/AA 7.30 ± 0.61; p = 0.0005), and HDL (GG: 52.80 ± 0.64 vs. AG/AA 49.54 ± 1.39; p = 0.0341). CONCLUSIONS: These data suggest a sex‐specific effect of Atrogin‐1 G202A genotype on serum insulin, HOMA, glucose and HDL levels in young Caucasian females. The GG genotype appears to be protective of hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. This SNP may affect regulation of the AKT insulin response pathway via a down‐regulation of Atrogin‐1. ACKNOWLEDGEMENT: This study was supported by NINDS ‐1R01NS040606.