Identification of the potential type 2 diabetes susceptibility genetic elements in South Asian populations

Batool, Hina; Mushtaq, Nada; Batool, Sana; Ullah, Fariha Inayat; Hamid, Arslan; Ali, Muhammad; Khan, Falak Shar; Butt, Asad Raza; Ashraf, Naeem Mahmood

doi:10.1016/j.mgene.2020.100771

Cited by 4 publications

(3 citation statements)

References 41 publications

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“… 23 Currently few genetic studies reporting T2DM-associated risk variants are available in South Asians. 24 T2DM is a major public health care issue in Pakistan. 25 Since genetic susceptibility plays a key role in T2DM etiology, it is important to carry out genetic studies to assess the genetic risk of T2DM in the Pakistani population.…”

Section: Introductionmentioning

confidence: 99%

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Jan¹,

Zakiullah²,

Khuda³

et al. 2023

JAFES

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Objective Recent GWAS largely conducted in European populations have successfully identified multiple genetic risk variants associated with Type 2 Diabetes Mellitus (T2DM). However, the effects conferred by these variants in the Pakistani population have not yet been fully elucidated. The objective of this study was to examine European GWAS-identified T2DM risk variants in the Pakistani Pashtun population to better understand the shared genetic basis of T2DM in the European and Pakistani cohorts. Methodology A total of 100 T2DM patients and 100 healthy volunteers of Pashtun ethnicity were enrolled in this study. Both groups were genotyped for 8 selected single nucleotide polymorphisms (SNPs) using the Sequenom MassARRAY ® platform. The association between selected SNPs and T2DM was determined by using appropriate statistical tests. Results Of the 8 studied SNPs, 5 SNPs, SLC30A8 / rs13266634 ( p =0.031, OR=2.13), IGF2BP2 / rs4402960 ( p =0.001, OR=3.01), KCNJ11 / rs5219 ( p =0.042, OR=1.78), PPARG / rs1801282 ( p =0.042, OR=2.81) and TCF7L2 / rs7903146 ( p =0.00006, 3.41) had a significant association with T2DM. SNP GLIS3 / rs7041847 ( p =0.051, OR=2.01) showed no sufficient evidence of association. SNPs KCNQ1 / rs2237892 ( p =0.140, OR=1.61) and HHEX/IDE / s1111875 ( p =0.112, OR=1.31) showed opposite allelic effects and were not validated for T2DM risk in the study population. Among the studied SNPs, TCF7L2 / rs7903146 showed the most significant association. Conclusion Our study finding indicates that selected genome-wide significant T2DM risk variants previously identified in European descent also increase the risk of developing T2DM in the Pakistani Pashtun population.

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Section: Introductionmentioning

confidence: 99%

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Jan¹,

Zakiullah²,

Khuda³

et al. 2023

JAFES

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“…In 2019, 1.5 million people worldwide died only due to diabetes [ 2 ]. In South Asia, Bangladeshi, Pakistani, Nepali, Bhutanese, Maldivian, Sri Lankan, and Singaporean populations showed a significant increase in T2D patients during the last three decades [ 3 ]. However, Indian populations showed the highest prevalence of diabetes, followed by the Chinese population.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, several genes have already been identified that are associated with T2D pathogenesis in SAP [ 4 , 5 , 14 ]. In Indian and Pakistani populations, TCF7L2 , FTO , PPARG2 , IRS1 , SLC30A8 , CDKN2A , HHEX , CDKAL1 , EXT2 , ADIPOQ , IGF2BP2 , WFS1 , LOC387761 , CAPN10 , CDKN2B , MTHFR , KCNJ11 , SGCG , ADAM30 , THADA , GCK , LOC646279 , TCF-2/ HNF1B , NOTCH2 , VEGFA , and HOMA-β genes were found to be associated with T2D pathogenesis [ 3 ]. Among SAP, HNF4A, HMG20A, VPS26A, GRB14, AP3S2, and ST6GAL1loci were found to be associated with T2D.…”

Section: Introductionmentioning

confidence: 99%

In silico identification and functional prediction of differentially expressed genes in South Asian populations associated with type 2 diabetes

Rabby,

Rahman,

Islam

et al. 2023

PLoS ONE

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Type 2 diabetes (T2D) is one of the major metabolic disorders in humans caused by hyperglycemia and insulin resistance syndrome. Although significant genetic effects on T2D pathogenesis are experimentally proved, the molecular mechanism of T2D in South Asian Populations (SAPs) is still limited. Hence, the current research analyzed two Gene Expression Omnibus (GEO) and 17 Genome-Wide Association Studies (GWAS) datasets associated with T2D in SAP to identify DEGs (differentially expressed genes). The identified DEGs were further analyzed to explore the molecular mechanism of T2D pathogenesis following a series of bioinformatics approaches. Following PPI (Protein-Protein Interaction), 867 potential DEGs and nine hub genes were identified that might play significant roles in T2D pathogenesis. Interestingly, CTNNB1 and RUNX2 hub genes were found to be unique for T2D pathogenesis in SAPs. Then, the GO (Gene Ontology) showed the potential biological, molecular, and cellular functions of the DEGs. The target genes also interacted with different pathways of T2D pathogenesis. In fact, 118 genes (including HNF1A and TCF7L2 hub genes) were directly associated with T2D pathogenesis. Indeed, eight key miRNAs among 2582 significantly interacted with the target genes. Even 64 genes were downregulated by 367 FDA-approved drugs. Interestingly, 11 genes showed a wide range (9–43) of drug specificity. Hence, the identified DEGs may guide to elucidate the molecular mechanism of T2D pathogenesis in SAPs. Therefore, integrating the research findings of the potential roles of DEGs and candidate drug-mediated downregulation of marker genes, future drugs or treatments could be developed to treat T2D in SAPs.

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An Update on the Epidemiology of Type 2 Diabetes

Tinajero

Malik

2021

Endocrinology and Metabolism Clinics of North America

238

115

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Identification of the potential type 2 diabetes susceptibility genetic elements in South Asian populations

Cited by 4 publications

References 41 publications

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

In silico identification and functional prediction of differentially expressed genes in South Asian populations associated with type 2 diabetes

An Update on the Epidemiology of Type 2 Diabetes

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