Diabetes and Genetics: A Relationship Between Genetic Risk Alleles, Clinical Phenotypes and Therapeutic Approaches

Sayed, Shomoita; Nabi, A.H.M. Nurun

doi:10.1007/5584_2020_518

Cited by 8 publications

(4 citation statements)

References 241 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the probe design of the targeted capture regions, we selected a total of 83 genes of interest where mutations had been reported to be causative for monogenic obesity or diabetes: MC3R, MC4R, SIM1, BDNF, MCHR1, LEP, LEPR, PCSK1, NTRK2 , and POMC for monogenic obesity ( Loos and Yeo, 2022 ); BBS1, BBS2, ARL6, BBS4 , and MKKS for BBS ( Florea et al., 2021 ); GLIS3, PLAGL1, PTF1A, INSR , and TBC1D for NDM ( Laimon et al, 2021 ); HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, KCNJ11 , and APPL1 for MODY ( Delvecchio et al., 2020 ); AKT2, AGPAT2, BSCL2, CAV1, LMNA, PPARG , and ZMPSTE24 for lipodystrophy ( Jéru, 2021 ); and some other associated genes for syndromic diabetes such as Wolfram syndrome, hemochromatosis, and Alström syndrome ( Zou et al., 2018 ; Meola, 2020 ; Kristan et al., 2021 ; Sayed and Nabi, 2021 ; Zhang et al., 2021 ; Prida et al., 2022 ). These genes can cause the disease alone or in combination.…”

Section: Methodsmentioning

confidence: 99%

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

Zhang

et al. 2023

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause. Here, we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes. We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing (WES) data available for 146 of these patients. The coverage of targeted gene panel sequencing was significantly higher than that of WES. The diagnostic yield in patients sequenced by the panel was 32.9% with subsequent WES leading to an additional three diagnoses with two novel genes. In total, 178 variants in 83 genes were detected in 146 patients by targeted sequencing. Three of the 178 variants were missed by WES, although the WES-only approach had a similar diagnostic yield. For the 335 samples only receiving targeted sequencing, the diagnostic yield was 32.2%. In conclusion, taking into account the lower costs, shorter turnaround time, and higher quality of data, targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES. Therefore, this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

show abstract

Section: Methodsmentioning

confidence: 99%

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

Zhang

et al. 2023

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

show abstract

“…Its global prevalence was about 8% in 2011 and is predicted to rise to 10% by 2030. 4 Prevalence of DM in our country is about 8.4 million or 10% of the total population. 5 Diabetes mellitus is an incurable disease but can be controlled by dietary modification (dietary control and regular physical exercise) and with or without anti-diabetic medicine.…”

Section: Introductionmentioning

confidence: 94%

Efficacy of Empagliflozin as Add-on Therapy in Patients with Uncontrolled Type 2 Diabetes Mellitus

Joysoual,

Ara,

Haque

et al. 2023

TAJ: J of Teachers Assoc

View full text Add to dashboard Cite

Background: Metformin is recommended as first-line pharmacotherapy for patients with type 2 Diabetes Mellitus (T2DM) who fail to achieve glycemic control through lifestyle modification. Metformin initially lowers blood glucose, but as diabetes progresses, it alone frequently fails to maintain glycemic control, and additional therapies are required. Empagliflozin is a potent and selective sodium-glucose co-transporter 2 (SGLT2) inhibitor that is effective in reducing blood sugar levels as monotherapy or add-on to existing therapy with significant improvements in glycemic control and weight. Materials & Methods: This quasi-experimental study was conducted in the Department of Pharmacology and Therapeutics in collaboration with Rajshahi Diabetic Association General Hospital, Rajshahi, for one year from January 2021 to December 2021 on 50 uncontrolled T2DM patients (glycosylated hemoglobin, HbA1c > 7.0 to ≤ 10.5%) for more than 12 weeks. The investigating drug, empagliflozin 10 mg (1 tablet) as a once-daily dose, was added to the ongoing treatment of each patient as 3rd line treatment and was followed up at 6 and 12 weeks. Results: The mean FBS at baseline was 10.8 mmol/L, which declined to 8.5 mmol/L at six weeks and then to 7.2 mmol/L after 12 weeks of intervention with Empagliflozin as add-on therapy in patients with uncontrolled T2DM. The overall reduction of FBS from baseline to 12 weeks of intervention was statistically significant (p < 0.001). Simultaneously the mean HbA1c also reduced from 9.4% to 7.7% after six weeks and to 7.1% after 12 weeks of intervention (p < 0.001). The mean systolic and diastolic blood pressures decreased from 129 mmHg to below 120 mmHg (p < 0.001) and 82.3 mmHg to below 80 mmHg (p = 0.029), respectively, after three months of intervention. Conclusion: Empagliflozin as add-on therapy responded well in patients with uncontrolled T2DM (previously treated with metformin combined with either sulfonylurea or DPP-4 inhibitors and/or supplemented by insulin) in achieving glycemic control. TAJ 2022; 36: No-1: 89-95

show abstract

“…The combination of different types of molecular data has indicated the genetic basis of diseases helping define the clinical status of patients ( 9 , 10 ). With this in mind, single nucleotide polymorphisms (SNPs), the most common type of mutation, have been predominant in the study of the link between genetic variations and pathologies ( 11 ). SNPs involve the replacement of one nucleotide for another, usually involving the substitution of cytosine (C) for thymine (T) ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms and protein levels in vocal fold leukoplakia: a systematic review

Campello

Lima-Silva

Lima

et al. 2022

Braz J Med Biol Res

View full text Add to dashboard Cite

Vocal fold leukoplakia (VFL) has a risk of malignant transformation. Therefore, patients can have symptoms such as dysphonia, vocal strain, difficulty breathing, and dysphagia. Additionally, there is a genetic predisposition that can be associated with genetic polymorphisms. We aimed to evaluate the influence of genetic polymorphisms and protein levels in the etiology of VFL. Our study followed the PRISMA checklist and was registered on PROSPERO database. The questions were: “Are genetic polymorphisms involved in the etiology of VFL? Are protein levels altered in patients with VFL?”. Eligibility criteria were case control studies that compared the presence of polymorphisms or/and protein levels of subjects diagnosed with VFL and healthy controls. Of the 905 articles retrieved, five articles with a total of 1038 participants were included in this study. The C allele of the single nucleotide polymorphisms (SNP)-819 T/C IL-10 , A allele of the SNP -592 A/C IL-10 , CT genotype of the SNP rs11886868 C/T BCL11A , GG genotype of the SNP rs4671393 A/G BCL11A , LL genotype, and L allele of (GT)n repeat polymorphisms of the HO-1 were risk factors for VFL development. Nevertheless, there was a lack of association between VFL and the -1082 A/G IL-10 , rs14024 CK-1 , and -309 T/G Mdm2 SNPs. The concentrations of the MDM2, BCL11A, and HO-1 proteins were modified, while IL-10 levels were normally expressed in these subjects. In conclusion, most markers evaluated in this review could be potential indicators to develop effective therapies, avoiding a malignant transformation of the lesion.

show abstract

Diabetes and Genetics: A Relationship Between Genetic Risk Alleles, Clinical Phenotypes and Therapeutic Approaches

Cited by 8 publications

References 241 publications

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

Efficacy of Empagliflozin as Add-on Therapy in Patients with Uncontrolled Type 2 Diabetes Mellitus

Genetic polymorphisms and protein levels in vocal fold leukoplakia: a systematic review

Contact Info

Product

Resources

About