Whole-genome re-sequencing for the identification of high contribution susceptibility gene variants in patients with type 2 diabetes

Sun, Xiaojuan; Sui, Weiguo; Wang, Xiaobing; Hou, Xianliang; Ou, Minglin; Dai, Yong; Xiang, Yueying

doi:10.3892/mmr.2016.5014

Cited by 6 publications

(5 citation statements)

References 45 publications

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“…This variant is present with a rare allele in one patient with MODY, but after validation it was not confirmed. Nevertheless, we tested this SNV in our groups because it had been found in patients with DM2 and seemed interesting [ 15 ]. In the DM2 group, a heterozygous rs806052 variant was identified in one male patient without a family history of diabetes mellitus.…”

Section: Main Textmentioning

confidence: 99%

Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia

et al. 2018

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ObjectiveEarlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.ResultsWe identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency < 1%) rs806052, rs143051164, and rs149840771 were genotyped in 126 cases of MODY, in 188 patients with type 2 diabetes mellitus (DM2), and 564 randomly selected Caucasian individuals in Russia. A heterozygous rs806052 variant was identified in one patient with DM2; c.1270T frequency was 0.003. Prevalence of rs143051164 c.844G was 0.003 in the control population and 0.004 and 0.003 in MODY and DM2 samples, respectively. Prevalence of rs149840771 c.2096A was 0.003 and 0.004 in the control population and among MODY patients, respectively. In DM2 patients, rs149840771 c.2096A was not identified. We did not detect any associations of rs806052, rs143051164, and rs149840771 with carbohydrate metabolism disorders among patients with MODY and DM2 in Russia.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3338-1) contains supplementary material, which is available to authorized users.

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Section: Main Textmentioning

confidence: 99%

Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia

et al. 2018

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“…No variants were found in the GCK gene. On the other hand, screening the HN-F1A gene sequences revealed six variants: three missenses and three synonymous variants (Table 1) [28][29][30][31][32][33][34][35][36].…”

Section: Resultsmentioning

confidence: 99%

Identification of Two Rare Homozygote Missense Variants in the IRS1 Gene in a Patient With Early Gestational Diabetes: A Case Study

et al. 2022

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Background: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and has a rising prevalence worldwide. Environmental and genetic factors contribute to GDM risk. Describing familial cases of GDM can help identify the disease's genetic components.Methods: Here, we report the case of an Emirati female patient affected with early GDM and familial history of diabetes with a significant level of insulin resistance. As a first step, we investigated the GCK and HNF1A gene sequences by direct sequencing and then performed a clinical exome sequencing (CES) of the patient's genomic DNA covering 6,670 genes.Results: Our findings showed the absence of any pathogenic variants in the GCK and HNF1A gene sequences. In addition, the CES excluded all maturity-onset diabetes of the young (MODY)-related genes. However, two rare homozygous variants in the insulin receptor substrate 1 (IRS1) gene were identified: p.Pro948Leu (gnomAD minor allele frequency (MAF) = 7.5 × 10 -5 ) and p.Arg1221Cys (gnomAD MAF = 5.6 × 10 -5 ). These variants were absent in a set of healthy Emirati individuals. Both variants are highly conserved among mammalians but have never previously been reported among the same haplotype or individual. p.Pro948Leu and p.Arg1221Cys are localized close to two important functional phosphorylation sites recognized by PI3K (hTyr941) and SHP2 (hTyr1229), respectively. Moreover, the independent and combined effect of the two variants on protein stability was predicted to be destabilizing. Conclusion:Our investigation emphasized the role of downstream regulators of insulin signaling in GDM pathophysiology and identified IRS1 as a candidate gene to explain chronic insulin resistance. In addition, the patient showed significant health improvement after lifestyle modifications and oral antidiabetic administration, even after withdrawing insulin injections.

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“…However, a limitation of this study was the insufficient sample size or different frequencies of different susceptible genes in different populations [ 29 , 30 , 31 , 32 ]. Therefore, further verification and improvement are needed in this regard.…”

Section: Discussionmentioning

confidence: 99%

Risk assessment of type 2 diabetes in northern China based on the logistic regression model

Liu

et al. 2021

THC

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BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex disease with high incidence and serious harm associated with polygenic determination. This study aimed to develop a predictive model so as to assess the risk of T2DM and apply it to health care and disease prevention in northern China. OBJECTIVE: Based on genotyping results, a risk warning model for type 2 diabetes was established. METHODS: Blood samples of 1042 patients with T2DM in northern China were collected. Multiplex polymerase chain reaction and high-throughput sequencing (NGS) techniques were used to design the amplification-based targeted sequencing panel to sequence the 21 T2DM susceptibility genes. RESULT: The related key gene KQT-like subfamily member 1 played an important role in the T2DM risk model, and single-nucleotide polymorphism rs2237892 was highly significant, with a P value of 1.2 × 10-5. CONCLUSIONS: Susceptibility genes in different populations were examined, and a model was developed to assess the risk-based genetic analysis. The performance of the model reached 92.8%.

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Whole-genome re-sequencing for the identification of high contribution susceptibility gene variants in patients with type 2 diabetes

Cited by 6 publications

References 45 publications

Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia

Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia

Identification of Two Rare Homozygote Missense Variants in the IRS1 Gene in a Patient With Early Gestational Diabetes: A Case Study

Risk assessment of type 2 diabetes in northern China based on the logistic regression model

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