Association of the IGF1 gene with fasting insulin levels

Willems, Sara M.; Cornes, Belinda K.; Brody, Jennifer A.; Morrison, Alanna C.; Lipovich, Leonard; Dauriz, Marco; Chen, Yuning; Liu, Ching‐Ti; Rybin, Denis; Gibbs, Richard A.; Pankow, James S.; Psaty, Bruce M.; Boerwinkle, Eric; Rotter, Jerome I.; Siscovick, David S.; Vasan, Ramachandran S.; Kaplan, Robert C.; Isaacs, Aaron; Dupuis, Josée; Duijn, Cornelia M. van; Meigs, James B.

doi:10.1038/ejhg.2016.4

Cited by 7 publications

(3 citation statements)

References 57 publications

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“…Similarly, Mannino et al also suggested that subjects carrying with the GG genotype of rs35767 showed lower insulin sensitivity and IGF-1 concentration compared with those carrying the A allele (Mannino et al 2013 ). The parameters of the rs5742694 polymorphism were reported for the first time as carriers of the TT genotype showing higher insulin sensitivity and lower insulin secretion (Willems et al 2016 ). However, no significant correlation was found between the rs5742694 polymorphism and IGF-1 level in serum.…”

Section: Discussionmentioning

confidence: 99%

The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China

et al. 2022

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Background Type 2 diabetes (T2DM) susceptibility varies among different populations and is affected by gene single nucleotide polymorphism (SNP). Insulin-like growth factor (IGF)-1 gene, which has many SNP loci, is involved in T2DM pathogenesis. However, the relationship of IGF-1 gene polymorphism with T2DM in Uyghur population is less studied. Objective To investigate the relationship between T2DM susceptibility and polymorphism of IGF-1 gene in Uyghur population of Xinjiang, China. Methods This study enrolled 220 cases (122 males (55.46%) and 98 females (44.54%); mean age of 53.40 ± 10.94 years) of T2DM patients (T2DM group) and 229 (124 males (54.15%) and 105 females (45.85%); mean age of 51.64 ± 10.48 years) healthy controls (control group). Biochemical indexes were determined. IGF-1 gene polymorphism was analyzed by SNP genotyping. Results The levels of TG, HDL, LDL, BUN, and Cr were statistically significant between the T2DM group and the control group. In terms of IGF-1 polymorphism, T2DM group had higher frequency of AA genotype (OR = 2.40, 95% CI = 1.19–4.84) and allele A (OR = 1.55, 95% CI = 1.17–2.06) of rs35767 loci, suggesting that rs35767 is related to the occurrence of T2DM. A total of 5 gene interaction models was obtained through analyzing the interaction of 5 SNP loci with the GMDR method. Among them, the two-factor model that included rs35767 locus and rs5742694 locus had statistical difference with a large cross-validation consistency (10/10). The combination of GG/CC, GA/AA, AA/AA, and AA/AC genotype was in high-risk group, whereas the combination of GG/AA, GG/AC, GA/AC and GA/CC genotype was in the low-risk group. The risk of T2DM in the high-risk group was 2.165 times than that of the low-risk group (OR = 2.165, 95% CI = 1.478–3.171). Conclusion TG, HDL, LDL, BUN, and Cr are influencing factors of T2DM in Uyghur population. The rs35767 locus of IGF-1 gene may be associated with T2DM in Uyghur population. The high-risk group composing of rs35767 locus and rs5742694 locus has a higher risk of T2DM.

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Section: Discussionmentioning

confidence: 99%

The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China

et al. 2022

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“…Subsequently, Huyghe et al also identified low-frequency coding variants associated with FPI at SGM2 and MADD gene in Finnish males [17]. Moreover, it is suggested that IGF-1 genetic variants were associated with FI in European ancestry [18]. Manning et al also observed that 6 SNPs in COBLL1-GRB14, IRS1, PPP1R3B, PDGFC, UHRF1BP1, and LYPLAL1 are correlated with the FI level [19].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of fasting proinsulin, fasting insulin, 2-hour postprandial proinsulin, and 2-hour postprandial insulin in Chinese Han people

Lin

Quan²,

Fang³

et al. 2022

Endokrynol Pol

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Introduction:Fasting proinsulin (FPI) and fasting insulin (FI) have been demonstrated to be associated with impaired b-cell function, T2DM, and insulin resistance. This genome-wide association study (GWAS) was performed to contribute to our understanding of the genetic basis of FPI, FI, 2-hour postprandial proinsulin (2hPI), and 2-hour postprandial insulin (2hI) of the pathophysiology of prediabetes in the Chinese population. Material and methods:The levels of fasting plasma glucose (FPG), FPI, FI, 2hPI, and 2hI were examined by an automatic biochemical analyser. The Applied Biosystems TM Axiom TM Precision Medicine Diversity Array, the Gene Titan Multi-Channel instrument, and Axiom Analysis Suite 6.0 Software were used for genotyping. Imputation was performed with IMPUTE 2.0 software from HapMap, 1000 Genomes Phase 3 as a reference panel. Results: Six single nucleotide polymorphisms (SNPs) in DLG1-AS1, SORCS1, and CTAGE11P for FPI, and 27 SNPs in ZNF718, MARCHF2, and HNRNPM for 2hPI reached genome-wide significance. Genome-wide significance was reached for associations of 6 SNPs in KRT71 to FI. Also, 14 SNPs in UBE2U, ABO, and GRID1-AS1 were genome-wide significant in their relationship with 2hI. Among these, the genetic loci of CTAGE11P, MARCHF2, KRT71, and ABO have the strongest association with FPI, 2hPI, FI, and 2hI. Conclusions: The genetic variants of CTAGE11P, MARCHF2, KRT71, and ABO are significantly correlated with FPI, 2hPI, FI, and 2hI, respectively, in Chinese Han people. These genetic variants may serve as new biomarkers for the prevention of prediabetes.

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“…The first hypothesis is that these SNPs might tag other variants in the IGF1 gene associated with insulin sensitivity and β cell function. In a recent study, the investigators revealed plenty of rare variants associated with fasting insulin levels that had not been previously described, by further study of the IGF1 gene [ 26 ]. Examination showed that the variants were located near the DNAseI hypersensitive sites and FOXA1 binding sites, indicating that they might have direct function because FOXA1 is a major transcriptional regulator factor in glucose homeostasis and insulin metabolism [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Microsatellite and Single Nucleotide Polymorphisms in the Insulin-Like Growth Factor 1 Promoter with Insulin Sensitivity and Insulin Secretion

Wang

et al. 2017

Med Sci Monit

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BackgroundTo investigate associations of the CA microsatellite and rs35767, rs5742612, and rs2288377 polymorphisms and the single nucleotide polymorphism (SNP) haplotypes with and without the CA microsatellite in the IGF1 promoter with insulin sensitivity and secretion.Material/MethodsThe CA microsatellite and SNPs were genotyped in 389 type 2 diabetes mellitus (T2DM) patients. A 75 g oral glucose tolerance test (OGTT) was given to all the participants. Associations of the genotypes and haplotypes with insulin sensitivity, insulin secretion, glucose tolerance, and insulin-like growth factor 1 (IGF1) were analyzed by ANCOVA (general linear model) and multiple linear regression, after controlling for gender, age, and BMI.ResultsThe CA microsatellite, rs35767 polymorphisms, and SNP haplotypes with or without CA showed no significant association with metabolic parameters. The C allele of rs5742612 was found to be associated with decreased insulin sensitivity (HOMA-S index, β=−0.131, P=0.008; fasting insulin level, β=0.022, P=0.006) and increased insulin secretion (HOMA-B index, β=0.099, P=0.008; insulin AUC, β=0.112, P=0.012). The linear regression model also indicated that the A allele of rs2288377 was associated with decreased insulin sensitivity (HOMA-S index, β=−0.159, P=0.001; fasting insulin, β=0.143, P=0.001) and increased insulin secretion (HOMA-B index, β=0.114, P=0.017; insulin AUC, β=0.042, P=0.002).ConclusionsThe CA microsatellite and rs35767 have no genotype-related difference in insulin sensitivity or secretion. The rs5742612 and rs2288377 polymorphisms are significantly associated with insulin biology, with the TT genotype exhibiting higher insulin sensitivity and lower insulin secretion compared with carriers of the C allele and A allele, respectively, mostly attributed to the direct functional roles of the two loci.

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Association of the IGF1 gene with fasting insulin levels

Cited by 7 publications

References 57 publications

The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China

The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China

Genome-wide association study of fasting proinsulin, fasting insulin, 2-hour postprandial proinsulin, and 2-hour postprandial insulin in Chinese Han people

Microsatellite and Single Nucleotide Polymorphisms in the Insulin-Like Growth Factor 1 Promoter with Insulin Sensitivity and Insulin Secretion

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