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PloS One 2015The potential association between the K121Q (A/C, rs1044498) polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1) gene and risk of diabetic... (Meta-Analysis)
Meta-Analysis Review
The potential association between the K121Q (A/C, rs1044498) polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1) gene and risk of diabetic kidney disease (DKD) has been investigated. Nevertheless, the effect of this variant on DKD risk is still under debate, and conflicting results have been reported. To this date, no meta-analysis has evaluated the association of the K121Q polymorphism with DKD. This paper describes the first meta-analysis conducted to evaluate whether the ENPP1K121Q polymorphism is associated with DKD. A literature search was conducted to identify all case-control or cross-sectional studies that evaluated associations between the ENPP1K121Q polymorphism and DKD. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for allele contrast, additive, dominant and recessive inheritance models. Seven studies were eligible for inclusion in the meta-analysis, providing data on 3571 type 1 or type 2 diabetic patients (1606 cases with DKD and 1965 diabetic controls without this complication). No significant heterogeneity was observed among the studies included in the meta-analysis when assuming different inheritance models (I² < 50% or P > 0.10 for the entire sample and after stratification by ethnicity). Meta-analysis results revealed significant associations between the K121Q polymorphism and risk of DKD in Asians and Europeans when assuming the different inheritance models analyzed. The most powerful association was observed for the additive model (OR = 1.74, 95% CI 1.27-2.38 for the total sample). In conclusion, the present meta-analysis detected a significant association between the ENPP1K121Q polymorphism and increased susceptibility of DKD in European and Asian populations.
Topics: Amino Acid Substitution; Diabetic Nephropathies; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Inheritance Patterns; Models, Genetic; Odds Ratio; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Pyrophosphatases; Risk Factors
PubMed: 25794151
DOI: 10.1371/journal.pone.0118416 -
BioMed Research International 2014The protooncogene PCPH was recently identified as being the ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5). This protooncogene is converted into an oncogene... (Review)
Review
The protooncogene PCPH was recently identified as being the ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5). This protooncogene is converted into an oncogene by a single base pair deletion, resulting in frame change and producing a premature stop codon, leading to a mutated protein (mt-PCPH) with only 27 kDa, which is much smaller than the original 47 kDa protein. Overexpression of the PCPH as well as the mutated PCPH increases the cellular resistance to stress and apoptosis. This is intriguing considering that the active form, that is, the oncogene, is the mutated PCPH. Several studies analyzed the expression of NTPDase5/mt-PCPH in a wide range of tumor cells and evaluated its role and mechanisms in cancer and other pathogenic processes. The main point of this review is to integrate the findings and proposed theories about the role played by NTPDase5/mt-PCPH in cancer progression, considering that these proteins have been suggested as potential early diagnostic tools and therapy targets.
Topics: Apoptosis; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Neoplasm Staging; Neoplasms; Oncogene Proteins; Pyrophosphatases; Sequence Deletion
PubMed: 25045656
DOI: 10.1155/2014/123010 -
Diabetes Apr 2008Functional studies suggest that the nonsynonymous K121Q polymorphism in the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) may confer susceptibility to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Functional studies suggest that the nonsynonymous K121Q polymorphism in the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) may confer susceptibility to insulin resistance; genetic evidence on its effect on type 2 diabetes, however, has been conflicting. We therefore conducted a new meta-analysis that includes novel unpublished data from the ENPP1 Consortium and recent negative findings from large association studies to address the contribution of K121Q to type 2 diabetes.
RESEARCH DESIGN AND METHODS
After a systematic review of the literature, we evaluated the effect of ENPP1 K121Q on diabetes risk under three genetic models using a random-effects approach. Our primary analysis consisted of 30 studies comprising 15,801 case and 26,241 control subjects. Due to considerable heterogeneity and large differences in allele frequencies across populations, we limited our meta-analysis to those of self-reported European descent and, when available, included BMI as a covariate.
RESULTS
We found a modest increase in risk of type 2 diabetes for QQ homozygotes in white populations (combined odds ratio [OR] 1.38 [95% CI 1.10-1.74], P = 0.005). There was no evidence of publication bias, but we noted significant residual heterogeneity among studies (P = 0.02). On meta-regression, 16% of the effect was accounted for by the mean BMI of control subjects. This association was stronger in studies in which control subjects were leaner but disappeared after adjustment for mean control BMI (combined OR 0.93 [95% CI 0.75-1.15], P = 0.50).
CONCLUSIONS
The ENPP1 Q121 variant increases risk of type 2 diabetes under a recessive model of inheritance in whites, an effect that appears to be modulated by BMI.
Topics: Adult; Aged; Amino Acid Substitution; Blood Glucose; Chromosome Mapping; Diabetes Mellitus, Type 2; Genes, Recessive; Humans; Insulin-Secreting Cells; Middle Aged; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Pyrophosphatases; White People
PubMed: 18071025
DOI: 10.2337/db07-1336