ARG1 single nucleotide polymorphisms rs2781666 and rs2781665 confer risk of Type 2 diabetes mellitus

Authors

  • Syed Fawad Ali Shah Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shehzad, Islamabad 45550, Pakistan
  • Tahir Iqbal Department of Internal Medicine, Shifa College of Medicine, Shifa International Hospital, H-8/4, Islamabad 44000, Pakistan
  • Nasreen Naveed The Diabetic Centre, Phulgran Stop Near Toll Plaza, Murree Express Way, Islamabad 635, Pakistan
  • Sumaira Akram Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shehzad, Islamabad 45550, Pakistan
  • Muhammad Arshad Rafiq Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shehzad, Islamabad 45550, Pakistan
  • Sabir Hussain Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shehzad, Islamabad 45550, Pakistan

DOI:

https://doi.org/10.17179/excli2018-1178

Keywords:

arginase-1, gene, polymorphism, association, Type 2 diabetes mellitus, genotyping

Abstract

Genetic polymorphisms mapped in the ARG1 locus (chr6:131894344-131905472) and their functional effects on type 2 diabetes mellitus (T2DM) have not been thoroughly elucidated to date. The present study aimed to investigate an association between variant alleles at ARG1 locus and T2DM in patients. Two ARG1 single nucleotide polymorphisms (SNPs) were characterized in a representative sample of 500 patients with T2DM and 500 healthy volunteers. Serum lipid profile was studied by spectrophotometric analysis, while serum arginase-1 concentrations were determined by an enzyme-linked immunosorbent assay. The regions, encompassing target SNPs (rs2781665 and rs2781666), were amplified by polymerase chain reaction and genotypes were assigned by restriction digestions. A statistically significant increase was observed in the serum hs-CRP and arginase-1 levels in the subjects with T2DM than in controls (P <0.0001; for each). The variant genotypes of rs2781666 and rs2781665 were significantly associated with T2DM when compared with controls (P< 0.0001). Moreover, type 2 diabetic patients showed higher frequencies of T allele at rs2781666 and rs2781665 compared to the controls (OR = 1.7; 95 % CI=1.31-2.13; P <0.0001, and OR = 1.9; 95 % CI=1.45-2.38; P <0.0001, respectively). Haplotype T-T (chr6: 131893247-131893559) mapped at rs2781665-A/T and rs2781666-G/T displays higher frequency in the subjects when compared to the healthy ethnically-matched control samples (P <0.0001). We wish to propose, the first ever observation to our knowledge that concluding high levels of arginase-1 and the ARG1 polymorphisms are possible causes to confer/augment the risk of T2DM in subjects originates in Pakistan.

Published

2018-08-27

How to Cite

Fawad Ali Shah, S., Iqbal, T., Naveed, N., Akram, S., Arshad Rafiq, M., & Hussain, S. (2018). ARG1 single nucleotide polymorphisms rs2781666 and rs2781665 confer risk of Type 2 diabetes mellitus. EXCLI Journal, 17, 847–855. https://doi.org/10.17179/excli2018-1178

Issue

Section

Original articles