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Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals.
Diabetes Care. 2006 Nov; 29(11):2489-97.DC

Abstract

OBJECTIVE

The provariant of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)gamma has been identified as a risk allele for type 2 diabetes. The purpose of the present study was to reveal a significant association with pre-diabetic phenotypes in nondiabetic individuals based on a systematic meta-analysis of all available published evidence.

RESEARCH DESIGN AND METHODS

We performed a classical meta-analysis of data from approximately 32,000 nondiabetic subjects in 57 studies to assess the effect of the Pro12Ala polymorphism on pre-diabetic traits.

RESULTS

In the global comparison, there were no differences in BMI, glucose, insulin, or homeostasis model assessment of insulin resistance between the Pro/Pro and X/Ala genotype. However, in the Caucasian subgroup, the X/Ala genotype was associated with significantly increased BMI. In the obese subgroup (BMI >30 kg/m(2)), fasting glucose (P = 0.041) and insulin resistance (by homeostasis model analysis) (P = 0.020) were significantly greater in the Pro/Pro group. In subjects with the homozygous Ala/Ala genotype, fasting insulin was significantly lower compared with the Pro/Pro genotype (P = 0.040, N(Ala/Ala) = 154).

CONCLUSIONS

Across all studies, the Pro12Ala polymorphism had no significant effect on diabetes-related traits. Only in selected subgroups, such as Caucasians and obese subjects, did we see an association of the Ala allele with greater BMI and greater insulin sensitivity. This demonstrates the importance for appropriate stratification of analyses by environmental or other genetic factors. Meta-analysis of Ala/Ala homozygotes more clearly demonstrated the association with greater insulin sensitivity of carriers of the Ala allele.

Authors+Show Affiliations

University of Leipzig, IIIrd Medical Department, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis

Language

eng

PubMed ID

17065690

Citation

Tönjes, Anke, et al. "Association of Pro12Ala Polymorphism in Peroxisome Proliferator-activated Receptor Gamma With Pre-diabetic Phenotypes: Meta-analysis of 57 Studies On Nondiabetic Individuals." Diabetes Care, vol. 29, no. 11, 2006, pp. 2489-97.
Tönjes A, Scholz M, Loeffler M, et al. Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care. 2006;29(11):2489-97.
Tönjes, A., Scholz, M., Loeffler, M., & Stumvoll, M. (2006). Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care, 29(11), 2489-97.
Tönjes A, et al. Association of Pro12Ala Polymorphism in Peroxisome Proliferator-activated Receptor Gamma With Pre-diabetic Phenotypes: Meta-analysis of 57 Studies On Nondiabetic Individuals. Diabetes Care. 2006;29(11):2489-97. PubMed PMID: 17065690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals. AU - Tönjes,Anke, AU - Scholz,Markus, AU - Loeffler,Markus, AU - Stumvoll,Michael, PY - 2006/10/27/pubmed PY - 2006/12/16/medline PY - 2006/10/27/entrez SP - 2489 EP - 97 JF - Diabetes care JO - Diabetes Care VL - 29 IS - 11 N2 - OBJECTIVE: The provariant of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)gamma has been identified as a risk allele for type 2 diabetes. The purpose of the present study was to reveal a significant association with pre-diabetic phenotypes in nondiabetic individuals based on a systematic meta-analysis of all available published evidence. RESEARCH DESIGN AND METHODS: We performed a classical meta-analysis of data from approximately 32,000 nondiabetic subjects in 57 studies to assess the effect of the Pro12Ala polymorphism on pre-diabetic traits. RESULTS: In the global comparison, there were no differences in BMI, glucose, insulin, or homeostasis model assessment of insulin resistance between the Pro/Pro and X/Ala genotype. However, in the Caucasian subgroup, the X/Ala genotype was associated with significantly increased BMI. In the obese subgroup (BMI >30 kg/m(2)), fasting glucose (P = 0.041) and insulin resistance (by homeostasis model analysis) (P = 0.020) were significantly greater in the Pro/Pro group. In subjects with the homozygous Ala/Ala genotype, fasting insulin was significantly lower compared with the Pro/Pro genotype (P = 0.040, N(Ala/Ala) = 154). CONCLUSIONS: Across all studies, the Pro12Ala polymorphism had no significant effect on diabetes-related traits. Only in selected subgroups, such as Caucasians and obese subjects, did we see an association of the Ala allele with greater BMI and greater insulin sensitivity. This demonstrates the importance for appropriate stratification of analyses by environmental or other genetic factors. Meta-analysis of Ala/Ala homozygotes more clearly demonstrated the association with greater insulin sensitivity of carriers of the Ala allele. SN - 0149-5992 UR - https://www.unboundmedicine.com/medline/citation/17065690/Association_of_Pro12Ala_polymorphism_in_peroxisome_proliferator_activated_receptor_gamma_with_Pre_diabetic_phenotypes:_meta_analysis_of_57_studies_on_nondiabetic_individuals_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=17065690 DB - PRIME DP - Unbound Medicine ER -