Screening of Type 2 Diabetes Mellitus Patients of Khyber Pakhtunkhwa for SLC30A8 (rs13266634) Variant Associated with Disease Susceptibility: SLC30A8 Variant Screening in Khyber Pakhtunkhwa T2DM Patients

Syed Shaukat Ali; Haji Bahadar; Haseenullah Shah; Sajid Ali; Monasib Khan; Fazli Khuda; Kiran Ijaz; Mohsin Raziq; . Zakiullah

doi:10.54393/pbmj.v7i03.1063

Authors

Syed Shaukat Ali Department of Pharmacy, University of Malakand, Chakdara, Pakistan
Haji Bahadar Institute of Pharmaceutical Sciences, Khyber Medical University, Peshawar, Pakistan
Haseenullah Shah Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
Sajid Ali Department of Biotechnology, Abdul Wali Khan University, Mardan, Pakistan
Monasib Khan Department of Pharmacy, University of Malakand, Chakdara, Pakistan
Fazli Khuda Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
Kiran Ijaz Institute of Pharmaceutical Sciences, Khyber Medical University, Peshawar, Pakistan
Mohsin Raziq Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
. Zakiullah Department of Pharmacy, University of Peshawar, Peshawar, Pakistan

DOI:

https://doi.org/10.54393/pbmj.v7i03.1063

Keywords:

SLC30A8, rs13266634 Variant, Type 2 Diabetes Mellitus (T2DM), Khyber Pakhtunkhwa

Abstract

Objective: To evaluate the association of the SLC30A8 rs13266634 variant with Type 2 Diabetes Mellitus (T2DM) susceptibility among patients in Khyber Pakhtunkhwa, Pakistan. Methods: A case-control study design was employed involving 100 each T2DM patients and healthy controls. Demographic and clinical features were recorded. The SLC30A8 rs13266634 variant was genotyped using PCR-RFLP. Statistical analyses, including binary logistic regression, were conducted to determine the association between the variant and T2DM, adjusting for age, gender, family history, and lifestyle factors. Results: The study cohort comprised predominantly males (65% in cases, 75% in controls) with a mean age of 53±9 years. T2DM patients exhibited a higher prevalence of concurrent conditions such as high blood pressure compared to controls. Genotyping revealed a significant association of the rs13266634 variant allele with T2DM. Individuals carrying variant CT and TT genotype had a 2.12 times higher risk (95% CI: 1.16-4.12, P=0.025) of T2DM compared to that of wild CC type. This association remained significant upon adjustment for confounders, with an adjusted odds ratio of 2.890 (95% CI: 2.233-9.76, P=0.02) for CT carriers. Conclusions: The rs13266634 variant in the SLC30A8 is significantly associated with an increased risk of T2DM in the Khyber Pakhtunkhwa population

References

Mukhtar Y, Galalain A, Yunusa U. A modern overview on diabetes mellitus: a chronic endocrine disorder. European Journal of Biology. 2020 Nov; 5: 1-4. doi:10.47672/ejb.409. DOI: https://doi.org/10.47672/ejb.409

da Rocha Fernandes J, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P, Cavan D, Makaroff LE et al. IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Research and Clinical Practice. 2016 Jul; 117: 48-54. doi: 10.1016/j.diabres.2016.04.016. DOI: https://doi.org/10.1016/j.diabres.2016.04.016

Peixoto-Barbosa R, Reis AF, Giuffrida FM. Update on clinical screening of maturity-onset diabetes of the young (MODY). Diabetology & Metabolic Syndrome. 2020 Dec; 12: 1-4. doi: 10.1186/s13098-020-00557-9. DOI: https://doi.org/10.1186/s13098-020-00557-9

Hilawe EH, Yatsuya H, Kawaguchi L, Aoyama A. Les différences entre les sexes dans la prévalence du diabète sucré, de la glycémie à jeun anormale et de l'intolérance au glucose en Afrique subsaharienne: Examen Systématique et Méta-Analyse. Bulletin of the World Health Organization. 2013 Sep; 91: 671-82D.

Dall TM, Yang W, Gillespie K, Mocarski M, Byrne E, Cintina I, Beronja K, Semilla AP, Iacobucci W, Hogan PF et al. The economic burden of elevated blood glucose levels in 2017: diagnosed and undiagnosed diabetes, gestational diabetes mellitus, and prediabetes. Diabetes Care. 2019 Sep; 42: 1661-8. doi.10.2337/dc18-1226. DOI: https://doi.org/10.2337/dc18-1226

Azeem S, Khan U, Liaquat A. The increasing rate of diabetes in Pakistan: A silent killer. Annals of Medicine and Surgery. 2022 Jul; 79: doi:10.1016/j.amsu.2022.103901. DOI: https://doi.org/10.1016/j.amsu.2022.103901

Soita DJ. The prevalence of impaired glucose tolerance and diabetes amongst the middle aged population of Bellville South Community, Cape Town, South Africa (Doctoral dissertation, Cape Peninsula University of Technology). 2009.

Chimeddamba O. Primary prevention of cardiovascular disease and diabetes in Mongolia: The role of primary care (Doctoral dissertation, Monash University). 2016.

Bukhsh A, Goh BH, Zimbudzi E, Lo C, Zoungas S, Chan KG, Khan TM et al. Type 2 diabetes patients' perspectives, experiences, and barriers toward diabetes-related self-care: a qualitative study from Pakistan. Frontiers in Endocrinology. 2020 Nov; 11: 534873. doi:10.3389/fendo.2020.534873. DOI: https://doi.org/10.3389/fendo.2020.534873

Bailey MJ, Naik NN, Wild LE, Patterson WB, Alderete TL. Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes. Gut Microbes. 2020 Sep; 11: 1188-202. doi:10.1080/19490976.2020.1749754. DOI: https://doi.org/10.1080/19490976.2020.1749754

Huang L and Tepaamorndech S. The SLC30 family of zinc transporters-a review of current understanding of their biological and pathophysiological roles. Molecular Aspects of Medicine. 2013 Apr; 34: 548-60. doi:10.1016/j.mam.2012.05.008. DOI: https://doi.org/10.1016/j.mam.2012.05.008

Back SH and Kaufman RJ. Endoplasmic reticulum stress and type 2 diabetes. Annual Review of Biochemistry. 2012 Jul; 81: 767-93. doi: 10.1146/annurev-biochem-072909-095555. DOI: https://doi.org/10.1146/annurev-biochem-072909-095555

DeFronzo RA and Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009 Nov; 32: S157. doi: 10.2337/dc09-S302. DOI: https://doi.org/10.2337/dc09-S302

Berry C, Lal M, Binukumar BK. Crosstalk between the unfolded protein response, MicroRNAs, and insulin signaling pathways: in search of biomarkers for the diagnosis and treatment of type 2 diabetes. Frontiers in Endocrinology. 2018 May; 9: 364990. doi:10.3389/fendo.2018.00210. DOI: https://doi.org/10.3389/fendo.2018.00210

Fahim NK, Negida A, Fahim AK. Sample size calculation guide-part 3: how to calculate the sample size for an independent case-control study. Frontiers in Emergency Medicine. 2019 Feb 20;3(2):e20-.

Gill PS, Narang J, Prasad M, Mohan H. Molecular detection of H1N1 virus by conventional reverse transcription PCR coupled with nested PCR. Sensors International. 2022 Jan; 3: 100178 doi:10.1016/j.sintl.2022.100178. DOI: https://doi.org/10.1016/j.sintl.2022.100178

Sirdah MM and Reading NS. Genetic predisposition in type 2 diabetes: a promising approach toward a personalized management of diabetes. Clinical Genetics. 2020 Dec; 98:525-47. doi:10.1111/cge.13772. DOI: https://doi.org/10.1111/cge.13772

Barroso I. Genetics of type 2 diabetes. Diabetic Medicine. 2005 May; 22: 517-35. doi:10.1111/j.1464-5491.2005.01550.x. DOI: https://doi.org/10.1111/j.1464-5491.2005.01550.x

De Villiers D, Potgieter M, Ambele MA, Adam L, Durandt C, Pepper MS et al. The role of reactive oxygen species in adipogenic differentiation. Stem cells: Biology and Engineering. 2018: 125-44. doi:10.1007/5584_2017_119. DOI: https://doi.org/10.1007/5584_2017_119

Shu XO, Long J, Cai Q, Qi L, Xiang YB, Cho YS, Tai ES, Li X, Lin X, Chow WH, Go MJ et al. Identification of new genetic risk variants for type 2 diabetes. PLoS Genetics. 2010 Sep; 6: e1001127. doi:10.1371/journal.pgen.1001127. DOI: https://doi.org/10.1371/journal.pgen.1001127

Sohani ZN, Deng WQ, Pare G, Meyre D, Gerstein HC, Anand SS et al. Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?. Diabetologia. 2014 Nov; 57: 2270-81. doi:10.1007/s00125-014-3354-1. DOI: https://doi.org/10.1007/s00125-014-3354-1