Download PDF
Horm Metab Res 2020; 52(12): 856-860
DOI: 10.1055/a-1204-5443
Endocrine Care

Role of the KCNJ Gene Variants in the Clinical Outcome of Type 1 Diabetes

Annalisa Blasetti
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Valeria Castorani
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Laura Comegna
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Simone Franchini
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Giovanni Prezioso
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Martina Provenzano
2   Molecular Genetics Unit, CeSI-Met, Chieti, Italy
,
Concetta Di Giulio
3   S.O.D. Pediatrics and Neonatology, Hospital of Senigallia, Senigallia, Italy
,
Daniela Iannucci
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Lorena Matonti
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Stefano Tumini
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Francesco Chiarelli
1   Department of Pediatrics, University of Chieti, Chieti, Italy
,
Liborio Stuppia
2   Molecular Genetics Unit, CeSI-Met, Chieti, Italy
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Diabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA’s loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

Key words

gene polimorphisms - K-ATP channels - type 1 diabetes - type 2 diabetes - insulin resistance - type 1.5 diabetes

Supplementary Material



Publication History

Received: 17 February 2020

Accepted after revision: 17 June 2020

Article published online:
21 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Haghvirdizadeh P, Mohamed Z, Abdullah NA. et al. KNCJ11: Genetic polymorphisms and risk of diabetes mellitus. J Diabetes Res 2015; 908152
    PubMedGoogle Scholar
  • 2 McTaggart JS, Clark RH, Ashcroft FM. The role of the K-ATP channel in glucose homeostasis in health and disease: more than meets the islet. J Physiol 2010; 588: 3201-3209
    CrossrefPubMedGoogle Scholar
  • 3 Ashcroft FM. K(ATP) channels and insulin secretion: A key role in health and disease. Biochem Soc Trans 2006; 34: 243-246
    CrossrefPubMedGoogle Scholar
  • 4 Schwanstecher C, Meyer U, Schwanster M. KIR6.2 Polymorphism Predisposes to Type 2 Diabetes by Inducing Overactivity of Pancreatic β-Cell ATP-Sensitive K+ Channels. Diabetes 2002; 51: 875-879
    CrossrefPubMedGoogle Scholar
  • 5 Florez JC, Jablonski KA, Kahn SE. et al. Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program. Diabetes 2007; 56: 531-536
    CrossrefPubMedGoogle Scholar
  • 6 Rabbani M, Sadeghi H, Moazen F. et al. Association of KCNJ11 (E23K) gene polymorphism with susceptibility to type 2 diabetes in Iranian patients. Adv Biomed Res 2015; 4: 1
    CrossrefPubMedGoogle Scholar
  • 7 Shaat N, Ekelund M, Lernmark Å. et al. Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Diabetologia 2005; 48: 2544-2551
    CrossrefPubMedGoogle Scholar
  • 8 De Jong VM, Zaldumbide A, Van Der Slik AR. et al. Post-transcriptional control of candidate risk genes for type 1 diabetes by rare genetic variants. Genes Immun 2013; 14: 58-61
    CrossrefPubMedGoogle Scholar
  • 9 Gong W, Xiao D, Ming G. et al. Type 2 diabetes mellitus-related genetic polymorphisms in microRNAs and microRNA target sites. J Diabetes 2014; 6: 279-289
    CrossrefPubMedGoogle Scholar
  • 10 Qin LJ, Lv Y, Huang QY. Meta-analysis of association of common variants in the KCNJ11-ABCC8 region with type 2 diabetes. Genet Mol Res 2013; 12: 2990-3002
    CrossrefPubMedGoogle Scholar
  • 11 Dehwah MAS, Xu A, Huang Q. MicroRNAs and type 2 diabetes/obesity. J Genet Genomics 2012; 39: 11-18
    CrossrefPubMedGoogle Scholar
  • 12 Alvarez ML, Di Stefano JK. The role of non-coding RNAs in diabetic nephropathy: Potential applications as biomarkers for disease development and progression. Diabetes Res Clin Pract 2013; 99: 1-11
    CrossrefPubMedGoogle Scholar
  • 13 Phani NM, Guddattu V, Bellampalli R. et al. Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: A case-control and meta-analysis study. PLoS One 2014; 9: 107021
    CrossrefPubMedGoogle Scholar
  • 14 Souza SW, Alcazar LP, Arakaki PA. et al. Polymorphism E23K (rs5219) in the KCNJ11 gene in Euro-Brazilian subjects with type 1 and 2 diabetes. Genet Mol Res 2017; 16
    PubMedGoogle Scholar
  • 15 Qiu L, Na R, Xu R. et al. Quantitative assessment of the effect of KCNJ11 gene polymorphism on the risk of type 2 diabetes. PLoS One 2014; 9: 93961
    CrossrefPubMedGoogle Scholar
  • 16 Gong B, Yu J, Li H. et al. The Effect of KCNJ11 polymorphism on the risk of type 2 diabetes: A global meta-analysis based on 49 case-control studies. DNA Cell Biol 2011; 31: 801-810
    CrossrefPubMedGoogle Scholar
  • 17 Li Q, Chen M, Zhang R. et al. KCNJ11 E23K variant is associated with the therapeutic effect of sulphonylureas in Chinese type 2 diabetic patients. Clin Exp Pharmacol Physiol 2014; 41: 748-754
    CrossrefPubMedGoogle Scholar
  • 18 Moritani M, Yokota I, Tsubouchi K. et al. Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 yr of age. Pediatr Diabetes 2013; 14: 112-120
    CrossrefPubMedGoogle Scholar
  • 19 Craig ME, Jefferies C, Dabelea D. et al. Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2014; 15: 4-17
    CrossrefPubMedGoogle Scholar
  • 20 Tamura K, Stecher G, Peterson D. et al. MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013; 30: 2725-2729
    CrossrefPubMedGoogle Scholar
  • 21 McDevitt HO. Characteristics of autoimmunity in type 1 diabetes and type 1.5 overlap with type 2 diabetes. Diabetes 2005; 54 (Suppl 2) S4-S10
    CrossrefPubMedGoogle Scholar
  • 22 Fourlanos S, Narendran P, Byrnes GB. et al. Insulin resistance is a risk factor for progression to Type 1 diabetes. Diabetologia 2004; 47: 1661-1667
    CrossrefPubMedGoogle Scholar
  • 23 Mrena S, Virtanen SM, Laippala P. et al. Models for predicting type 1 diabetes in siblings of affected children. Diabetes Care 2006; 29: 662-667
    CrossrefPubMedGoogle Scholar
  • 24 Dabelea D, Pihoker C, Talton J. et al. SEARCH for Diabetes in Youth Study. Diabetes Care 2011; 34: 1628-1633
    CrossrefPubMedGoogle Scholar
  • 25 Cervin C, Lyssenko V, Bakhtadze E. et al. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes 2008; 57: 1433-1437
    CrossrefPubMedGoogle Scholar
  • 26 Juneja R, Hirsch IB, Naik RG. et al. Islet cell antibodies and glutamic acid decarboxylase antibodies, but not the clinical phenotype, help to identify type 1 1/2 diabetes in patients presenting with type 2 diabetes. Metabolism 2001; 50: 1008-1013
    CrossrefPubMedGoogle Scholar
  • 27 Speliotes EK, Willer CJ, Berndt SI. et al. Association analyses of 29,796 individuals reveal eighteen new loci associated with body mass index. Nat Genet 2010; 42: 937-948
    CrossrefPubMedGoogle Scholar