Dataset Information

"Pesto" Mutation: Phenotypic and Genotypic Characteristics of Eight GCK/MODY Ligurian Patients.

ABSTRACT: Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes mellitus (DM) that accounts for around 2-5% of all types of diabetes. Autosomal dominant inheritance in pathogenic variations of 14 genes related to β-cell functions can lead to monogenic types of diabetes. In Italy, GCK/MODY is the most frequent form and it is caused by mutations of the glucokinase (GCK). Patients with GCK/MODY usually have stable mild fasting hyperglycaemia with mildly elevated HbA1c levels and rarely need pharmacological treatment. Molecular analysis of the GCK coding exons was carried out by Sanger sequencing in eight Italian patients. All the probands were found to be heterozygous carriers of a pathogenic gross insertion/deletion c.1279_1358delinsTTACA; p.Ser426_Ala454delinsLeuGln. It was previously described for the first time by our group in a large cohort of Italian GCK/MODY patients. The higher levels of HbA1c (6.57% vs. 6.1%), and the higher percentage of patients requiring insulin therapy (25% vs. 2%) compared to the previously studied Italian patients with GCK/MODY, suggest that the mutation discovered could be responsible for a clinically worse form of GCK/MODY. Moreover, as all the patients carrying this variant share an origin from the same geographic area (Liguria), we postulate a possible founder effect and we propose to name it the "pesto" mutation.

SUBMITTER: Salina A

PROVIDER: S-EPMC9961661 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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"Pesto" Mutation: Phenotypic and Genotypic Characteristics of Eight GCK/MODY Ligurian Patients.

Salina Alessandro A Bassi Marta M Aloi Concetta C Strati Marina Francesca MF Bocciardi Renata R d'Annunzio Giuseppe G Maghnie Mohamad M Minuto Nicola N

International journal of molecular sciences 20230217 4

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes mellitus (DM) that accounts for around 2-5% of all types of diabetes. Autosomal dominant inheritance in pathogenic variations of 14 genes related to β-cell functions can lead to monogenic types of diabetes. In Italy, GCK/MODY is the most frequent form and it is caused by mutations of the glucokinase (GCK). Patients with GCK/MODY usually have stable mild fasting hyperglycaemia with mildly elevated HbA1c levels and rarely ...[more]

PMID: 36835446

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Project description:AimsGlucokinase-maturity-onset diabetes of the young (GCK-MODY) is the most common monogenic diabetes in China. We have previously reported on the low levels of high-sensitivity C-reactive protein (hsCRP) in patients with GCK-MODY. In this study, we further explored the correlation between the serum lipid profiles and hsCRP levels of patients with different types of diabetes. We also proposed to determine the possible mechanism of macrovascular protection in GCK genetic variants.MethodsThe serum lipid profiles of the GCK-MODY group (n = 50) were compared with those of the hepatocyte nuclear factor-1 alpha (HNF1A)-MODY group (n = 19), the type 1 diabetes (T1D) group (n = 50), and the type 2 diabetes (T2D) group (n = 54). The associations between the lipid compositions and the hsCRP levels in each group were also explored.ResultsElevated levels of high-density lipoprotein cholesterol (HDL-C) were found in the GCK-MODY group (1.5 ± 0.27) compared with the T1D (1.2 ± 0.47, p < 0.01) and T2D (1.3 ± 0.3, p < 0.01) groups. On the other hand, a significantly lower LDL-C level (2.4 ± 0.69) in the GCK-MODY group compared with the T1D (2.7 ± 0.72, p < 0.01) and T2D (2.9 ± 0.68, p < 0.01) groups was also noted. A lower ratio of triglyceride to HDL-C (TG/HDL) and a lower hsCRP level were also found in the GCK-MODY group [TG/HDL = 0.38 (0.25-0.52), hsCRP = 0.2 mg/L (0.16-0.37)] compared with the T1D group [(TG/HDL = 0.56 (0.39-1.29), hsCRP = 0.56 mg/L (0.39-1.29), p < 0.01] and the T2D group [(TG/HDL = 1.6 (1.1-2.68), hsCRP = 1.11 mg/L (0.66-2.34), p < 0.01]. Although patients with HNF1A-MODY showed similar hsCRP levels [0.17 (0.08-0.52), p > 0.05] compared with the patients in the GCK-MODY group, they had higher TG levels [1.01 (0.66-1.76), p < 0.05] and TG/HDL ratios [0.84 (0.56-1.31), p < 0.05]. Analysis of the correlations between the hsCRP levels and lipid profiles of each group confirmed that the LnhsCRP (natural logarithm-transformed hsCRP level) was positively correlated with the LnTG (natural logarithm-transformed TG) (r = 0.352, p = 0.011) and the Ln(TG/HDL) ratio (r = 0.283, p = 0.047) only in individuals with GCK-MODY.ConclusionsIndividuals harboring GCK variants have the characteristics of protective lipid profiles manifested as a higher level of HDL-C and a lower level of LDL-C compared with type 1 and 2 diabetes milletus (T1DM and T2DM, respectively) patients. In addition, lower ratios of TG/HDL were found to be associated with the inhibition of secretion of hsCRP, even when adjusted for the HbA1c levels in patients with GCK-MODY. It is suggested that the protective effect of macrovascular complications in GCK-MODY patients might partly be due to their unique lipid profiles associated with the suppression of inflammation.

Dataset Information

"Pesto" Mutation: Phenotypic and Genotypic Characteristics of Eight GCK/MODY Ligurian Patients.

Publications

"Pesto" Mutation: Phenotypic and Genotypic Characteristics of Eight GCK/MODY Ligurian Patients.

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