Association between 14 bp insertion/deletion HLA-G functional polymorphism and insulin resistance in a cohort of Italian children with obesity

Pediatr Diabetes. 2018 Dec;19(8):1357-1361. doi: 10.1111/pedi.12768. Epub 2018 Sep 25.

Abstract

Background: The non-classical HLA-class I molecule-g (HLA-G) gene shows a deletion/insertion (del/ins) polymorphism of a 14-base-pair sequence (14 bp) in the exon 8 at the 3' untranslated region. The presence of the 14 bp insertion allele has been associated to lower soluble HLA-G protein production, a protein with anti-inflammatory activities. So far, no studies have investigated the relationship between HLA-G 14 bp del/ins polymorphism and metabolic features of obese children and adolescents. We aimed to assess if the HLA-G ins/del polymorphism, and in particular the HLA-G ins/ins genotype determining lower sHLA-G production, is associated to insulin resistance (evaluated by homeostasis model assessment [HOMA]) in a population of obese children.

Methods: We enrolled 574 obese children and adolescents. Anthropometric and laboratory data were collected. The white blood cell (WBC) count was evaluated as surrogate marker of inflammation. C-reactive protein (CRP) was available in 48 patients. HOMA was calculated. Patients were genotyped for the HLA-G del/ins polymorphism.

Results: Subjects carrying the HLA-G ins/ins genotype, presented with higher HOMA, WBC and CRP values, compared to del/ins and del/del genotypes (P ≤ 0.0009, ≤0.02 and ≤0.0001, respectively). Comparison of the regression line slopes, performed for HOMA and WBC on the basis of HLA-G genotypes, showed that subjects carrying the HLA-G ins/ins genotype presented with a stronger correlation between HOMA and WBC, compared to the other genotypes (Model r2 3.13%, P ≤ 0.006).

Conclusions: We showed a strong association between HLA-G 14 bp ins/ins genotype and HOMA in obese children and adolescents. This association could be hypothetically modulated by subclinical inflammation.

Keywords: HLA-G; HOMA; children; chronic inflammation; obesity.

MeSH terms

  • Adolescent
  • Asymptomatic Diseases
  • Case-Control Studies
  • Child
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HLA-G Antigens / genetics*
  • Humans
  • INDEL Mutation*
  • Inflammation / complications
  • Inflammation / genetics
  • Insulin Resistance / genetics*
  • Italy / epidemiology
  • Male
  • Pediatric Obesity / epidemiology
  • Pediatric Obesity / genetics*
  • Polymorphism, Genetic*

Substances

  • HLA-G Antigens