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Genetic association of insulin receptor substrate-1 (IRS-1, rs1801278) gene with insulin resistant of type 2 diabetes mellitus in a Pakistani population

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Abstract

Insulin resistance (IR), a pathological condition of type 2 diabetes mellitus (T2DM) is characterized by an inability of body’s tissue to respond the secreted or administered insulin, a necessary step for cellular glucose transportation. The prevalence of insulin resistance progresses with age, especially in overweight people with central obesity. Insulin receptor substrates (IRS) are important molecular proteins in the insulin signalling pathway, where IRS-1 plays a key function in cells insulin sensitivity. The common mutation (rs1801278; r.2963G > A: Gly972Arg) of the IRS-1 gene occurs when residue glycine changes to arginine at codon 972. The objective of this study was to detect the genetic association of rs1801278 polymorphism of the IRS-1 gene with insulin resistance in type 2 diabetes from the Lahore region of Pakistan. A total of 322 subjects (161 cases and 161 healthy individuals) were included. DNA was isolated for detection of the genotype distribution and allele frequencies by PCR–RFLP. The results showed a significant difference in the genotype distribution and allele frequency between the T2DM cases and controls for single nucleotide polymorphism (SNP) rs1801278 (OR 17.61, 95% CI 8.06–38.4, p < 0.001). In conclusion, association between rs1801278 polymorphism of the IRS-1 gene and insulin resistance in T2DM has been established in a Pakistani population.

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Acknowledgements

We would like to thank Mr. Ali Amar Research fellow and Miss. Osheen Sajjad Lecturer of Department of Human Genetics for their assistance. We wish to thank Mrs. Amara Lab Manager of the department of Pharmacology for continuous support.

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Authors and Affiliations

  1. Department of Pharmacology, University of Health Sciences, Khayaban-e-Jamia Punjab Street, Lahore, 54600, Pakistan

    Abdullah Abdo Albegali & Muhammad Shahzad

  2. Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, 54600, Pakistan

    Saqib Mahmood

  3. Department of Clinical Laboratory Sciences, Jouf University, Sakaka, 2014, Kingdom of Saudi Arabia

    Muhammad Ikram Ullah

Authors
  1. Abdullah Abdo Albegali
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  2. Muhammad Shahzad
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  3. Saqib Mahmood
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  4. Muhammad Ikram Ullah
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Contributions

MS and SM: conceived and designed the study: AAA: collected the samples from subjects and performed laboratory experiments, AAA, MIU and MR: data integration and statistical analyses and its interpretation; AAA and MIU: draft the manuscript, MS, SM and MR: edit and approve the manuscript.

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Correspondence to Muhammad Shahzad.

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Albegali, A.A., Shahzad, M., Mahmood, S. et al. Genetic association of insulin receptor substrate-1 (IRS-1, rs1801278) gene with insulin resistant of type 2 diabetes mellitus in a Pakistani population. Mol Biol Rep 46, 6065–6070 (2019). https://doi.org/10.1007/s11033-019-05041-w

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  • DOI: https://doi.org/10.1007/s11033-019-05041-w

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