Exploring single nucleotide polymorphisms previously related to obesity and metabolic traits in pediatric-onset type 2 diabetes

Acta Diabetol. 2017 Jul;54(7):653-662. doi: 10.1007/s00592-017-0987-9. Epub 2017 Apr 12.

Abstract

Aims: To evaluate the association of 64 obesity-related polymorphisms with pediatric-onset type 2 diabetes and other glucose- and insulin-related traits in Mexican children.

Methods: Case-control and case-sibling designs were followed. We studied 99 patients with pediatric-onset type 2 diabetes, their siblings (n = 101) without diabetes, 83 unrelated pediatric controls and 137 adult controls. Genotypes were determined for 64 single nucleotide polymorphisms, and a possible association was examined between those genotypes and type 2 diabetes and other quantitative traits, after adjusting for age, sex and body mass index.

Results: In the case-pediatric control and case-adult control analyses, five polymorphisms were associated with increased likelihood of pediatric-onset type 2 diabetes; only one of these polymorphisms (CADM2/rs1307880) also showed a consistent effect in the case-sibling analysis. The associations in the combined analysis were as follows: ADORA1/rs903361 (OR 1.9, 95% CI 1.2; 3.0); CADM2/rs13078807 (OR 2.2, 95% CI 1.2; 4.0); GNPDA2/rs10938397 (OR 2.2, 95% CI 1.4; 3.7); VEGFA/rs6905288 (OR 1.4, 95% CI 1.1; 2.1) and FTO/rs9939609 (OR 1.8, 95% CI 1.0; 3.2). We also identified 16 polymorphisms nominally associated with quantitative traits in participants without diabetes.

Conclusions: ADORA/rs903361, CADM2/rs13078807, GNPDA2/rs10938397, VEGFA/rs6905288 and FTO/rs9939609 are associated with an increased risk of pediatric-onset type 2 diabetes in the Mexican population.

Keywords: Adolescents; Children; Metabolic syndrome; Single nucleotide polymorphisms; Type 2 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Asian People / genetics
  • Body Mass Index
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / genetics*
  • Obesity / complications
  • Obesity / genetics*
  • Obesity / metabolism
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Siblings
  • Young Adult