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      The association of ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus in European, American, and African populations: A meta-analysis

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          Abstract

          Introduction:

          Several studies regarding the association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus (T2DM) showed inconsistent results. This study aimed to investigate the association of ENPP1 K121Q gene polymorphism with T2DM risk using meta-analysis. The study was limited to the American, European, and African populations.

          Methods:

          PubMed and Embase databases were searched for eligible publications. The following information was extracted from each study: Name of first author, publication year, country of origin, sample size of cases and controls, and size of each allele. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between ENPP1 K121Q gene polymorphism and T2DM risk were assessed using random or fixed effect model. A comprehensive meta-analysis (CMA) 2.0 was used to analyze the data.

          Results:

          Nineteen studies (17717 cases/28022 controls) on the association between ENPP1 K121Q gene polymorphism and T2DM risk were included in this meta-analysis. The results indicated that the ENPP1 K121Q gene polymorphism was associated with increased T2DM risk (Q vs. K genetic model, OR 95% CI = 1.11 [1.02–1.22], p = 0.014; QQ vs. KK + KQ, OR 95% CI = 1.14 [1.01–1.23], p = 0.039) and decreased T2DM risk (K vs. Q, OR 95% CI = 0.90 [0.82–1.00], p = 0.014; KK vs. KQ + QQ, OR 95% CI = 0.89 [0.80–0.98], p = 0.024).

          Conclusions:

          The results indicate that the ENPP1 K121Q gene polymorphism is associated with the risk of T2DM in the American, European, and African populations.

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          Most cited references42

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          Diagnosis and classification of diabetes mellitus.

          (2004)
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            Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

            Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.
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              Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes.

              We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.
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                Author and article information

                Journal
                JHS
                Journal of Health Sciences
                University of Sarajevo Faculty of Health Studies (Bosnia )
                2232-7576
                1986-8049
                2016
                : 6
                : 2
                : 76-86
                Affiliations
                [1]Medical Research Unit, School of Medicine, University of Syiah Kuala, Banda Aceh, Indonesia
                Author notes
                Corresponding author: Jonny Karunia Fajar, Medical Research Unit, School of Medicine, University of Syiah Kuala, Jl. Tanoeh Abe, Darussalam, Banda Aceh 23111, Indonesia, Tel.: +62(0)81235522287, Fax: +62(0)651 7551843,
                Article
                JHS-6-76
                10.17532/jhsci.2016.358
                cb901bfd-4e8d-493c-9a97-4606c8343278
                Copyright: © 2016 Jonny Karunia Fajar

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 June 2016
                : 4 July 2016
                Categories
                REVIEW ARTICLE

                Nursing,General medicine,Medicine,Molecular medicine,Life sciences
                genetic polymorphism,ENPP1 K121Q gene polymorphism,insulin resistance,type 2 diabetes mellitus,meta-analysis

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