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The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study
- Source :
- Acta Diabetologica. 50:429-436
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (β = -1.27; p = 0.001) and HOMA-IR (β = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
Genotype
Cross-sectional study
Endocrinology, Diabetes and Metabolism
Disease
p53 polymorphism codon 72
Logistic regression
Polymorphism, Single Nucleotide
HOMA-IR
Body Mass Index
Endocrinology
Insulin resistance
Risk Factors
Diabetes mellitus
Internal medicine
Genetic model
Internal Medicine
medicine
Homeostasis
Humans
Codon
Aged
diabetes mellitu
business.industry
Fasting
General Medicine
Middle Aged
medicine.disease
Lipids
Cross-Sectional Studies
type 2
Diabetes Mellitus, Type 2
Female
Insulin Resistance
Tumor Suppressor Protein p53
Energy Metabolism
business
Body mass index
Subjects
Details
- ISSN :
- 14325233 and 09405429
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Acta Diabetologica
- Accession number :
- edsair.doi.dedup.....22634d666a675fcbfa91c409e208a9ec