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The Role of the PGC1α Gly482Ser Polymorphism in Weight Gain due to Intensive Diabetes Therapy

By Samir S. Deeb and John D. Brunzell


The Diabetes Control and Complications Trial (DCCT) involved intensive diabetes therapy of subjects with type 1 diabetes mellitus (T1DM) for an average period of 6.5 years. A subset of these subjects gained excessive weight. We tested for association of polymorphisms in 8 candidate genes with the above trait. We found the Gly482Ser polymorphism in the peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) to be significantly associated with weight gain in males (P = .0045) but not in females. The Ser allele was associated with greater weight gain than the Gly allele (P = .005). Subjects with a family history of type 2 diabetes mellitus (T2DM) were more common among those who gained excessive weight. We conclude that T2DM and the Gly482Ser polymorphism in PGC1α contribute to the effect of intensive diabetes therapy on weight gain in males with T1DM

Topics: Research Article
Publisher: Hindawi Publishing Corporation
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Provided by: PubMed Central

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  2. (2002). A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to type II diabetes,”
  3. (2001). A genome-wide scan for abdominal fat assessed by computed tomography
  4. (2007). A genomewide association study of type 2 diabetes in finns detects multiplesusceptibilityvariants,”Science,vol.316,no.5829,pp. 1341–1345,
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  6. (1998). A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity,”
  7. (2001). A transgenic model of visceral obesity and the metabolic syndrome,”
  8. (2004). Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk,”
  9. (2003). An autoregulatory loop controls peroxisome proliferatoractivated receptor γ coactivator 1α expression in muscle,”
  10. (1998). An autosomal genomic scan for loci linked to prediabetic phenotypes in pima indians,”
  11. (2002). C.Menzaghi,T.Ercolino,R.D.Paola,etal.,“Ahaplotypeatthe adiponectin locus is associated with obesity and other features oftheinsulinresistancesyndrome,”Diabetes,v ol.51,no .7,pp .
  12. (2004). C825T polymorphism of the G protein β3 subunit is associated with obesity but not with insulin sensitivity,”
  13. (2004). Common polymorphisms of the PPAR-γ2( Pro12Ala)a n d PGC-1α (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes
  14. (2003). Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of
  15. (2002). Effect of the (C825T) Gβ3 polymorphism on adrenoceptormediated lipolysis in human fat cells,”
  16. (2000). G protein β3 subunit 825T allele, hypertension, obesity, and diabetic nepropathy,”
  17. (2004). Genes and pathophysiology of type 2 diabetes: more than just the Radle cycle all over again,”
  18. (2002). Genetic variation in the gene encoding adiponectin is associated with an increased risk
  19. (2006). Increased risk of obesity associated with the variant allele of the PPARGC1A Gly482Ser polymorphism in physically inactiveelderlymen,”
  20. (2001). Minireview: 11β-hydroxysteroid dehydrogenase type 1—a tissue-specific amplifier of glucocorticoid action,”
  21. (2004). Multiple environmental and genetic factors influence skeletal muscle PGC-1α and PGC-1β gene expression in twins,”
  22. (2001). Mutation analysis of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to type II diabetes mellitus,”
  23. (2008). New insights into the genetics of body weight,”
  24. (1987). olewski,E.J .K osinski,J .H.W arram,etal.,“M agnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus,”
  25. (1998). P u r n e l l ,J .E .H o k a n s o n ,S .M .M a r c o v i n a
  26. (2003). P u r n e l l ,R .K .D e v ,M .W .S t e ffes, et al., “Relationship of family history of type 2 diabetes, hypoglycemia, and autoantibodies to weight gain and lipids with intensive and conventional therapy in the diabetes control and complications trial,”
  27. (2002). Peroxisome proliferator-activated receptor-γ coactivator-1 gene locus: associations with obesity indices in middle-aged women,”
  28. (2003). Peroxisome proliferatoractivated receptor-γ coactivator 1α (PGC-1α): transcriptional coactivator and metabolic regulator,”
  29. (2003). PGC1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes,”
  30. (2004). Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition,”
  31. (2000). Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome,”
  32. R.Rosmond,Y.C.Chagnon,G.Holm,etal.,“Aglucocorticoid receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitaryadrenalaxis,”ObesityResearch,vol.8,no.3,pp.211–218,2000.
  33. (2001). Restoration of insulin-sensitiveglucosetransporter(GLUT4)geneexpression in muscle cells by the transcriptional coactivator
  34. (1999). s t e r b a u e r ,H .O b e r k o fl e r ,F .K r e m p l e r ,a n dW .P a t s c h , “Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression,”
  35. (2000). The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes,”
  36. (1993). The Diabetes Control and Complications Trial Research Group, “The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus,” The New England
  37. (2006). The Gly482Ser variant of the PPARGC1 gene is associated with type 2 diabetes mellitus in northern Chinese,
  38. (2001). Tissue-specific dysregulation of cortisol metabolism in human obesity,”

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