Insulin gene VNTR genotype is associated with insulin sensitivity and secretion in infancy

Bazaes, Rodrigo; Petry, Clive J.; Ong, Kenneth; Ávila, Alejandra; Mericq, Verónica

doi:10.1046/j.1365-2265.2003.01890.x

Cited by 21 publications

(16 citation statements)

References 21 publications

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“…A recent report demonstrated higher insulin secretion during an IVGTT among infants with the class III/III genotype. However, the class III/III carriers were more insulin-resistant, and increased insulin secretion might thus be a compensatory mechanism to insulin resistance [34]. The difference in beta cell response to an intravenous glucose load could also be due to the difference in age in the various study populations.…”

Section: Discussionmentioning

confidence: 98%

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

et al. 2004

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Aims/hypothesis. The class III allele of the variablenumber-of-tandem-repeats polymorphism located 5′ of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. Methods. We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middleaged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes.Results. There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middleaged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. Conclusions/interpretation. The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.

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Section: Discussionmentioning

confidence: 98%

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

et al. 2004

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“…Although it remains controversial, a direct effect of class III alleles on beta cells has previously been demonstrated in non-diabetic infants [13], adult patients with type 1 diabetes onset after 35 years of age [14] and obese nondiabetic women [15], while others have failed to show such an association [16].…”

Section: Discussionmentioning

confidence: 99%

Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function

et al. 2005

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Aims/hypothesis: The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS). We investigated the association between INS VNTR class III alleles (-23HphIA/T) and both insulin antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes. Materials and methods: To estimate C-peptide levels and autoantibody presentation, patients underwent a mealstimulated C-peptide test 1, 6, and 12 months after diagnosis. The insulin -23HphIA/T variant was used as a marker of class III alleles and genotyped by PCR-RFLP. Results: The insulin antibody titres at 1 and 6 months were significantly lower in the class III/III and class I/III genotype groups than in the class I/I genotype group (p = 0.01). Class III alleles were also associated with residual beta cell function 12 months after diagnosis and independently of age, sex, BMI, insulin antibody titres, and HLA-risk genotype group (p = 0.03). The C-peptide level was twice as high among class III/III genotypes as in class I/I and class I/III genotypes (319 vs 131 and 166 pmol/l, p=0.01). Furthermore, the class III/III genotype had a 1.1% reduction in HbA 1 c after adjustment for insulin dose (p = 0.04). Conclusions/interpretation: These findings suggest a direct connection in vivo between INS VNTR class III alleles, a decreased humoral immune response to insulin, and preservation of beta cell function in recentonset type 1 diabetes.

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“…The variation in VNTR was shown to influence transcriptional activity of the gene in vitro and regulates INS transcription levels in cadaveric adult [11] and fetal human pancreas [12], and in pancreatic beta cells [13]. Le Fur S. et al [14] revealed that the polymorphisms of INS VNTR are associated in vivo with a trend for lower insulin and higher glucose levels, while Bazaes et al [15] reported an association between INS VNTR genotype and both insulin sensitivity and secretion in infancy. However, recent clinical studies that attempted to confirm these associations have produced conflicting results.…”

Section: Introductionmentioning

confidence: 99%

Lack of association of INS VNTR polymorphism with polycystic ovary syndrome: a meta-analysis

Song

Luo

Peng

et al. 2014

J Assist Reprod Genet

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Purpose An association between the INS VNTR polymorphisms and polycystic ovary syndrome (PCOS) susceptibility has been reported in previous studies, but the results were inconsistent. This study was conducted to explore this association using meta-analysis. Methods PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched according to predefined criteria for all relevant studies published up to August 2013. Four genetic models, together with odds ratios (ORs) and 95 % confidence intervals (CI), were calculated. Subgroup analyses were performed by ethnicity, anovulatory PCOS, and Hardy-Weinberg equilibrium (HWE) in the controls. Results In total, 13 case-control studies, including 1,767 cases and 4,108 controls, were included. No significant association was detected in overall population in all models (III/III Conclusions This meta-analysis revealed no significant association between INS VNTR polymorphisms and the risk of PCOS in the overall population, while it supported that variance may be associated with susceptibility to PCOS with anovulation. Further confirmation is needed from more welldesigned and larger studies.

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Insulin gene VNTR genotype is associated with insulin sensitivity and secretion in infancy

Abstract: Significant associations between INS VNTR genotype and both insulin sensitivity and secretion were apparent in infancy; these might interact with childhood appetite and nutrition to impact the development of childhood obesity and insulin resistance.

Cited by 21 publications

References 21 publications

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function

Lack of association of INS VNTR polymorphism with polycystic ovary syndrome: a meta-analysis

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