Dataset Information

Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population.

ABSTRACT: AIMS/INTRODUCTION:Neonatal diabetes mellitus is created by alterations in the genes responsible for beta-cell mass and/or function. The present study aimed to evaluate the genetic variants in the insulin gene (INS) in four Chinese infants aged <12 months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by INS mutations. MATERIALS AND METHODS:The complete coding sequences of KCNJ11, ABCC8 and INS were detected using Sanger sequencing. The pathogenicity of the mutations was determined based on the American College of Medical Genetics and Genomics, and the structure of wild-type and mutant proteins was predicted using the web-based tool, Phyre2. RESULTS:One novel mutation (p.I99_C100insSI) and three previously reported variants (p.G32S, p.R89C and p.C96R) in INS were identified in four infants with early-onset diabetes. All the mutations in the four patients were de novo. Except for mutation R89C, which causes permanent neonatal diabetes mellitus through the addition of an additional cysteine residue at the cleavage site of the A chain and C-peptide, the other three mutations affected disulfide bonds. The patients had diabetes with marked hyperglycemia or diabetic ketoacidosis, and were then treated with exogenous insulin. Mutations in crucial regions of the INS might give rise to diabetes with varying severity. CONCLUSIONS:This study enriches our awareness of the mutant spectrum in INS, and suggests the important role of INS in the development of permanent neonatal diabetes mellitus.

SUBMITTER: Fu J

PROVIDER: S-EPMC7232282 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population.

Fu Junling J Wang Tong T Li Mingmin M Xiao Xinhua X

Journal of diabetes investigation 20191025 3

<h4>Aims/introduction</h4>Neonatal diabetes mellitus is created by alterations in the genes responsible for beta-cell mass and/or function. The present study aimed to evaluate the genetic variants in the insulin gene (INS) in four Chinese infants aged <12 months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by INS mutations.<h4>Materials and methods</h4>The complete coding sequences of KCNJ11, ABCC8 and INS were detect ...[more]

PMID: 31605659

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Project description:ObjectiveTo explore the relationship between angiotensin-converting enzyme 2 (ACE2) genetic variants and gestational diabetes mellitus (GDM) in a southern Chinese population.MethodsPotential functional variants (rs2106809, rs6632677, and rs2074192) of ACE2 were selected and genotyped in 566 GDM patients and 710 normal pregnaõncies in Guilin, China. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between genetic variant and GDM risk, and then the false positive report probability, multifactor dimensional reduction (MDR), and bioinformatics tools were used to confirm the significant association in the study.ResultsAfter adjusting for age and prepregnancy body mass index, logistic regression analysis showed that ACE2 rs6632677 was significantly associated with a decreased risk of GDM (CC vs. GG: adjusted OR = 0.09, 95% CI: 0.01 - 0.71, P = .023; GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46 - 0.99, P = .048; and CC vs. GG/GC: adjusted OR = 0.09, 95% CI = 0.01 - 0.72, P = .024), whereas rs2074192 was associated with increased GDM risk (TT vs. CC/CT: adjusted OR = 1.38, 95% CI = 1.08 - 1.75, P = .009). Furthermore, we found that rs6632677 interacted with SBP (P interaction = .043) and FPG (P interaction = .021) and rs2074192 interacted with HDL-c (P interaction = .029) and LDL-c (P interaction = .035) to influence the GDM risk of the individual. In the MDR analysis, the rs6632677 was the best one-locus model, and the three-loci model was the best interaction model to predict GDM risk. In addition, functional analysis confirmed that rs2074192 may regulate the splicing process of ACE2 gene.ConclusionACE2 gene variants are significantly associated with the risk of GDM via gene-gene and gene-environment combinations. The rs2074192 C > T affects the splicing of the ACE2 gene, which may be a potential mechanism leading to the changed susceptibility of an individual female during pregnancy to GDM.

Project description:Aims/introductionTo investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals.Materials and methodsFrom the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history.ResultsThe age- and sex-standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01-, 2.67- and 6.37-fold greater, and the risks of impaired glucose metabolism were 1.28-, 1.65- and 3.45-fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (PMHvsPH = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for β-cell function (β[SE] = -0.0910[0.0334], P = 0.0065), insulinogenic index (-0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [-0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P < 0.0001) and Matsuda Index (-0.1566[0.0243], P < 0.0001), but the effects were stronger than those of MH (PMHvsPH = 0.0431, 0.0054).ConclusionsMH and PH differentially influence the risks for diabetes, insulin secretion, and insulin resistance in the Chinese population, suggesting they participate in the pathogenesis of diabetes through different mechanisms.

Dataset Information

Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population.

Publications

Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population.

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