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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma


IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

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2191-0251
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Volume 32, Issue 1

Issues

No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova

Adela Chirita-Emandi
  • Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
  • “Louis Turcanu” Emergency Hospital for Children, Timisoara, Romania
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/ Diana Munteanu
  • Centre of Reproductive Health and Medical Genetics, Institute of Mother and Child, Chisinau, Republic of Moldova
  • Endocrinology Department, University of Medicine and Pharmacy “Nicolae Testemițanu”, Chisinau, Republic of Moldova
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/ Nicoleta Andreescu
  • Corresponding author
  • Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
  • “Louis Turcanu” Emergency Hospital for Children, Timisoara, Romania
  • Email
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/ Paul Tutac
  • Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
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/ Corina Paul
  • Second Pediatric Clinic, Department of Paediatrics – University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
  • Pediatric Department, Clinical County Hospital, Timisoara, Romania
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/ Iulian Puiu Velea
  • Second Pediatric Clinic, Department of Paediatrics – University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
  • Pediatric Department, Clinical County Hospital, Timisoara, Romania
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/ Agneta Maria Pusztai
  • Department of Anatomy, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
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/ Victoria Hlistun
  • Centre of Reproductive Health and Medical Genetics, Institute of Mother and Child, Chisinau, Republic of Moldova
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/ Chiril Boiciuc
  • Centre of Reproductive Health and Medical Genetics, Institute of Mother and Child, Chisinau, Republic of Moldova
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/ Victoria Sacara
  • Centre of Reproductive Health and Medical Genetics, Institute of Mother and Child, Chisinau, Republic of Moldova
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/ Lorina Vudu
  • Endocrinology Department, University of Medicine and Pharmacy “Nicolae Testemițanu”, Chisinau, Republic of Moldova
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/ Natalia Usurelu
  • Centre of Reproductive Health and Medical Genetics, Institute of Mother and Child, Chisinau, Republic of Moldova
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/ Maria Puiu
  • Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
  • “Louis Turcanu” Emergency Hospital for Children, Timisoara, Romania
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Published Online: 2018-12-18 | DOI: https://doi.org/10.1515/jpem-2018-0288

Abstract

Background

Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova.

Methods

Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome.

Results

Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478–0.724; odds ratio [OR] range=1.924–4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance.

Conclusions

The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.

Keywords: children; GCKR; GCK1; IGF1; insulin resistance; IRS1; KCTD1; PPARG

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About the article

Corresponding author: Dr. Nicoleta Andreescu, Center of Genetics Medicine, University of Medicine and Pharmacy “Victor Babes”, P-ta Eftimie Murgu nr. 2, Timisoara 300041, Romania

aAdela Chirita-Emandi and Diana Munteanu contributed equally to this work.


Received: 2018-03-01

Accepted: 2018-11-17

Published Online: 2018-12-18

Published in Print: 2019-01-28


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Academy of Science of Moldova (Program 16.80012.04.33F), Center of Genomic Medicine of the University of Medicine and Pharmacy “Victor Babes” Timisoara (POSCCE-A2-O2.2.1-2013-1), Internal Competition, University of Medicine and Pharmacy “Victor Babes” Timisoara (Program II-C4-TC-2016), Romania-Moldova bilateral project funded by the Academy of Science of Moldova and ANCS from Romania (Project 16.80012.04.33F).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 32, Issue 1, Pages 33–39, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2018-0288.

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