Back to Search
Start Over
Genetic epistasis of adiponectin and PPAR?2 genotypes in modulation of insulin sensitivity: a family-based association study
- Source :
- Diabetologia. 46:977-983
- Publication Year :
- 2003
- Publisher :
- Springer Science and Business Media LLC, 2003.
-
Abstract
- Genetic interactions in modulating the phenotypes of a complex trait, such as insulin sensitivity, were usually taken for granted. However, this has not been commonly shown. Previous studies have suggested that both PPARgamma2 and adiponectin genes could influence insulin sensitivity. Therefore it is likely that they could modulate insulin sensitivity through gene to gene interactions.We genotyped 1793 subjects of Chinese and Japanese descendents from 601 hypertensive families recruited in Sapphire study for a T94G in the adiponectin gene exon 2 and the PPARgamma2 Pro12Ala polymorphisms. Serum insulin concentrations and insulin resistance index (HOMA(IR)) were used as the markers of insulin sensitivity.We found that the T allele of adiponectin gene was associated with a higher Ins60 and higher area under curve of insulin (AUCi) in OGTT utilizing all subjects in a mixed model that corrected for family effects. Important interactions between adiponectin and PPARgamma2 genotypes were found in fasting insulin concentrations (Ins0), insulin concentrations at 2-h (Ins120) in OGTT and insulin resistance index (HOMA(IR)). The main effects of the PPARgamma2 genotypes were in the plasma glucose concentrations in OGTT. In contrast, the main effects of adiponectin genotypes were in every insulin variable, including Ins0, Ins60, Ins120, AUCi and HOMA(IR). The subjects carrying the adiponectin G allele and the PPARgamma2 Ala12 allele seemed to be more insulin sensitive.These results showed that adiponectin is a genetic factor associated with insulin sensitivity. Interactions with PPARgamma2 genotypes modified this association.
- Subjects :
- China
medicine.medical_specialty
Genotype
Endocrinology, Diabetes and Metabolism
Mutation, Missense
Receptors, Cytoplasmic and Nuclear
Biology
medicine.disease_cause
Polymorphism, Single Nucleotide
Asian People
Gene Frequency
Japan
Gene interaction
Internal medicine
Internal Medicine
medicine
Humans
Insulin
Family
Allele frequency
Gene
Genetics
Mutation
Adiponectin
Proteins
Epistasis, Genetic
Exons
Glucose Tolerance Test
Phenotype
Endocrinology
Amino Acid Substitution
Area Under Curve
Hypertension
Intercellular Signaling Peptides and Proteins
Epistasis
Insulin Resistance
Transcription Factors
Subjects
Details
- ISSN :
- 14320428 and 0012186X
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Diabetologia
- Accession number :
- edsair.doi.dedup.....b88314e7af84ed7fc13fc7206ccd78e8