Maturity-onset diabetes of the young in children with incidental hyperglycemia: a multicenter Italian study of 172 families.
Ontology highlight
ABSTRACT: Objective
To investigate the prevalence of maturity-onset diabetes of the young (MODY) in Italian children with incidental hyperglycemia.Research design and methods
Among 748 subjects age 1-18 years with incidental hyperglycemia, minimal diagnostic criteria for MODY were met by 172 families. Mutational analyses of the glucokinase (GCK) and hepatocyte nuclear factor 1alpha (HNF1A) genes were performed.Results
We identified 85 GCK gene mutations in 109 probands and 10 HNF1A mutations in 12 probands. In GCK patients, the median neonatal weight and age at the first evaluation were lower than those found in patients with HNF1A mutations. Median fasting plasma glucose and impaired fasting glucose/impaired glucose tolerance frequency after oral glucose tolerance testing were higher in GCK patients, who also showed a lower frequency of diabetes than HNF1A patients.Conclusions
GCK mutations are the prevailing cause of MODY (63.4%) when the index case is recruited in Italian children with incidental hyperglycemia.
SUBMITTER: Lorini R
PROVIDER: S-EPMC2752915 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
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Project description:BackgroundThe molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population.MethodsAll diabetic patients (N = 565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n = 46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n = 30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n = 486) and non-diabetic controls (n = 263) were included. Genetic analyses for the HNF1A gene p.S487 N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group.Resultsp.S487 N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p > 0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR = 1.68, 95% CI: [1. 21-2.13]; p = 0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR = 1.56, 95% CI: [1. 14-2.57]; p = 0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (β = 1.45, 95% CI: [1. 2-4.2]; p = 0.036).ConclusionsThe HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.
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