Evidence for interaction between PPARG Pro12Ala and PPARGC1A Gly482Ser polymorphisms in determining type 2 diabetes intermediate phenotypes in overweight subjects.
Exp Clin Endocrinol Diabetes
; 117(9): 455-9, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19536736
BACKGROUND: The peroxisome proliferator-activated receptor-gamma ( PPARG) Pro12Ala and the PPARG co-activator-1alpha ( PPARGC1A) Gly482Ser polymorphisms (SNPs) have been associated with type 2 diabetes mellitus (T2DM) risk. We hypothesized that independent and interactive effects of the PPARG Pro12Ala and PPARGC1A Gly482Ser polymorphisms influence T2DM intermediate phenotypes. MATERIAL AND METHODS: PPARG Pro12Ala and PPARGC1A Gly482Ser SNPs were studied in 680 non diabetic subjects who underwent a 75 g oral glucose tolerant test (OGTT). Glucose and insulin plasma levels in the fasting state and derived from the OGTT were included in the present study. RESULTS: We found significant independent effects of the PPARG and PPARGC1A variants on fasting insulin levels (p=0.02 for both), HOMA-IR (p=0.03 and p=0.02, respectively), insulin area under the curve (AUC) (p=0.007 and p=0.006, respectively) and 2-h glucose levels (p=0.02 for PPARGC1A). Furthermore, significant gene-gene interactions were found for fasting insulin, HOMA-IR and insulin AUC (p=0.03 for all). Carriers of the PPARGC1A Gly allele who were also PPARG Ala-carriers had higher fasting insulin levels (p=0.02), HOMA-IR (p=0.01) and insulin AUC (p=0.01) compared to the Ser/Ser-Ala+genotype combination, whereas no differences between the PPARGC1A genotypes among the PPARG Pro/Pro carriers were observed. CONCLUSION: Together, these results showed that PPARG Pro12Ala and PPARGC1A Gly482Ser variants are associated, alone and in interaction, with insulin and glucose homeostasis and suggest that gene-gene interactions should be taken into account in candidate gene studies of T2DM to identify subjects with markedly different risks of developing the disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
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Factores de Transcripción
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PPAR gamma
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Diabetes Mellitus Tipo 2
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Proteínas de Choque Térmico
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Exp Clin Endocrinol Diabetes
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Alemania