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Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans

Bailetti, Diego ; Sentinelli, Federica ; Prudente, Sabrina ; Cimini, Flavia Agata ; Barchetta, Ilaria ; Totaro, Maria ; Di Costanzo, Alessia ; Barbonetti, Arcangelo ; Leonetti, Frida ; Cavallo, Maria Gisella ; Baroni, Marco Giorgio

International journal of molecular sciences, 2022-01, Vol.23 (3), p.1221 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans
Autor: Bailetti, Diego ; Sentinelli, Federica ; Prudente, Sabrina ; Cimini, Flavia Agata ; Barchetta, Ilaria ; Totaro, Maria ; Di Costanzo, Alessia ; Barbonetti, Arcangelo ; Leonetti, Frida ; Cavallo, Maria Gisella ; Baroni, Marco Giorgio
Assuntos: Adult ; Biomarkers ; Blood pressure ; Carrier Proteins - genetics ; Cholesterol ; Cohort Studies ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - pathology ; Disease ; disposition index ; Evaluation ; extremes ; Female ; Genes ; Genetic analysis ; Genetic Predisposition to Disease ; Genomes ; Glucose ; Glucose tolerance ; GTPase-Activating Proteins - genetics ; High density lipoprotein ; High-Throughput Nucleotide Sequencing ; Humans ; Insulin ; Insulin Resistance ; Insulin Secretion ; Male ; Metabolism ; Middle Aged ; next-generation sequencing ; Obesity ; Obesity - physiopathology ; Pathogenesis ; Plasma ; Polymorphism, Single Nucleotide ; RNA-Binding Proteins - genetics ; Secretion ; Statistical analysis ; targeted resequencing ; Variables
É parte de: International journal of molecular sciences, 2022-01, Vol.23 (3), p.1221
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SourceType-Scholarly Journals-1
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Descrição: Type 2 diabetes is characterized by impairment in insulin secretion, with an established genetic contribution. We aimed to evaluate common and low-frequency (1-5%) variants in nine genes strongly associated with insulin secretion by targeted sequencing in subjects selected from the extremes of insulin release measured by the disposition index. Collapsing data by gene and/or function, the association between disposition index and nonsense variants were significant, also after adjustment for confounding factors (OR = 0.25, 95% CI = 0.11-0.59, = 0.001). Evaluating variants individually, three novel variants in and , out of eight reaching significance singularly, remained associated after adjustment. Constructing a genetic risk model combining the effects of the three variants, only carriers of the and variants were significantly associated with a reduced probability to be in the lower, worst, extreme of insulin secretion (OR = 0.223, 95% CI = 0.105-0.473, < 0.001). Observing a high number of normal glucose tolerance between carriers, a regression posthoc analysis was performed. Carriers of genetic risk model variants had higher probability to be normoglycemic, also after adjustment (OR = 2.411, 95% CI = 1.136-5.116, = 0.022). Thus, in our southern European cohort, nonsense variants in all nine candidate genes showed association with better insulin secretion adjusted for insulin resistance, and we established the role of and in modulating insulin secretion.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans

Bailetti, Diego ; Sentinelli, Federica ; Prudente, Sabrina ; Cimini, Flavia Agata ; Barchetta, Ilaria ; Totaro, Maria ; Di Costanzo, Alessia ; Barbonetti, Arcangelo ; Leonetti, Frida ; Cavallo, Maria Gisella ; Baroni, Marco Giorgio

Switzerland: MDPI AG

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