Exploring the Relationship between SLC30A8 Gene Polymorphism and Type 2 Diabetes Susceptibility in District Vehari, Pakistan | [Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences • 2024]

Author(s):

1. Fatima Ghafoor: Institute of Microbiology and Molecular Genetics (IMMG), The University of Punjab,Lahore,Pakistan

2. Samreen Riaz: Institute of Microbiology and Molecular Genetics (IMMG), The University of Punjab,Lahore,Pakistan

Abstract:

Type 2 diabetes mellitus (T2DM) is estimated to aflict 537 million individuals globally and has reached an epidemic scale. These global estimates are to develop innovative preventive and treatment methods and to put these methods into action. To investigate if SLC30A8 gene polymorphisms can be used to predict the onset of T2DM in residents of Punjab, Pakistan, two groups were established based on prospective follow-up of appropriate population samples. Males made up 29.6% and women 70.4% of the T2DM unit. Deoxyribonucleic acid (DNA) was separated. Polymerase chain reaction or PCR was used for genotyping, and real-time PCR was then conducted. The statistical analysis was performed utilizing the statistical package SPSS 16.0 software program. The SLC30A8 gene genotype TT rs13266634 was linked to an increased risk of type 2 diabetes mellitus (T2DM) (relative risk - RR 1.51, 95% confidence interval - CI 1.11 - 2.05, p = 0.008). A protective benefit against T2DM was linked to the SLC30A8 gene's CC genotype, rs13266634 (RR 0.57, 95% CI 0.35 - 0.92, p = 0.026). The T2DM group comprised 442 individuals in the District Vehari. The average age at the time of the initial screening was 56.2 ± 6.7 years. 531 individuals without diabetes were chosen to serve as controls; their average age was 56.1 ± 7.1 years. In the control group, the frequencies of single nucleotide polymorphisms (abbreviated as SNP) match the expected frequencies as per the Hardy-Weinberg equilibrium. The SLC30A8 gene's rs13266634 polymorphism shows its correlation with the likelihood of developing T2DM and can be a potential candidate for a diabetes risk score.

Page(s): 235-242

DOI: 10.53560/PPASB(61-2)1056

Published: Journal: Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences, Volume: 61, Issue: 2, Year: 2024

Keywords:

type 2 diabetes mellitus , single nucleotide polymorphism , Genotype , rs13266634 , SLC30A8

References:

[1] Tariq O.,Rosten C.,Huber J. .2024 .Cultural Influences on Making Nutritional Adjustments in Type 2 Diabetes in Pakistan: The Perspectives of People Living with Diabetes and Their Family Members. Qualitative Health Research 34, (6) : 562-578.

[2] Azeem S.,Khan U.,Liaquat A. .2022 .The increasing rate of diabetes in Pakistan: A silent killer. Annals of Medicine and Surgery, 79 : 103901.

[3] Grover A.,Sharma K.,Gautam S.,Gautam S.,Gulati M.,Singh S. K. Diabetes .2021 .and its complications: Therapies available, anticipated and aspired. Current Diabetes Reviews, 17(4) : 397-420.

[4] Hua F. .2020 .New insights into diabetes mellitus and its complications: a narrative review. Annals of Translational Medicine, 1689(24) : .

[5] Taheri R.,Kazerouni F.,Mirfakhraei R.,Kalbasi S.,Shahrokhi S.Z.,Rahimipour A. .2022 .The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic eficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study. Gene, 823 : 146382.

[6] Jamwal A. .2020 .Systematic Review on Medicaments Used in Management of Diabetes Mellitus. International Journal of Pharmacy and Pharmaceutical Sciences, 12(8) : 21-29.

[7] Ahmad E.,Lim S.,Lamptey R.,Webb D. R.,Davies M. J. .2022 .Type 2 diabetes. The Lancet, 400(10365) : 1803-1820.

[8] Dedov I.I.,Shestakova M.V.,Vikulova O.K.,Zheleznyakova A.V.,Isakov M.A. .2021 .Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register. Diabetes Mellitus, 24(3) : 204-221.

[9] Sikhayeva N.,Iskakova A.,Saigi-Morgui N.,Zholdybaeva E.,Eap C.B.,Ramanculov E. .2017 .Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study. BMC Medical Genetics, 18(1) : 1-13.

[10] Mustafina S.V.,Rymar O.D.,Ivanova A.A.,Shcherbakova L.V.,Bobak M.,Maljutina S.K.,Voevoda M.I.,Maksimov V.N. .2022 .Association of polymorphisms of genes SLC30A8 and MC4R with the prognosis of the development of type 2 diabetes mellitus. Diabetes Mellitus, 25(3) : 215-225.

[11] Suthon S.,Tangjittipokin W. .2024 .Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus. International Journal of Molecular Sciences, 25(4) : .

[12] Giacconi R.,Malavolta M.,Chiodi L.,Boccoli G.,Costarelli L.,Bonfigli A.R.,Galeazzi R.,Piacenza F.,Basso A.,Gasparini N.,Nisi L.,Testa R.,Provinciali M. .2018 .ZnT8 Arg325Trp polymorphism influences zinc transporter expression and cytokine production in PBMCs from patients with diabetes. Diabetes Research and Clinical Practice, 144 : 102-110.

[13] Koepsell H. .2021 .General overview of organic cation transporters in brain. Organic Cation Transporters in the Central Nervous System, 266 : 1-39.

[14] Benny P.,Ahn H.J.,Burlingame J.,Lee M.J.,Miller C.,Chen J.,Urschitz J. .2021 .Genetic risk factors associated with gestational diabetes in a multi-ethnic population. Plos One, 0261137(12) : .

[15] Zeng Q.,Tan B.,Han F.,Huang X.,Huang J.,Wei Y.,Guo R .2023 .Association of solute carrier family 30 A8 zinc transporter gene variations with gestational diabetes mellitus risk in a Chinese population. Frontiers in Endocrinology, 14 : 1159714.

[16] Sun P.,Saeedi S.,Karuranga M.,Pinkepank K.,Ogurtsova B.B.,Duncan D.J.,Magliano. IDF Diabetes D.J. .2022 .Atlas: Global, regional and countrylevel diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183 : 109119.

[17] Jamshaid T. .2023 .. Diabetes Mellitus-The Epidemic of 21 Century. Esculapio-Journal of Services Institute of Medical Sciences, 19(01) : 1-2.

[18] K.G. .2023 .Jhaveri. Linagliptin and metformin in Indian patients with type 2 diabetes: Safety and eficacy study. International Journal of Life Sciences, Biotechnology and Pharma Research, 12(3) : 1587-1591.

[19] Chimienti F.,Devergnas S.,Favier A.,Seve M. .2004 .Identification and cloning of a β-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. Diabetes, 53(9) : 2330-2337.

[20] Chimienti F.,Devergnas S.,Pattou F.,Schuit F.,Garcia-Cuenca R.,Vandewalle B.,Seve M. .2006 .In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion. Journal of Cell Science, 119(20) : 4199-4206.

[21] Sladek R.,Rung J.,Dina C.,Shen L.,Serre D.,Boutin P.,Vincent D.,Belisle A.,Hadjadj S.,Balkau B.,Heude B.,Hudson T.J.,Montpetit A.,Pshezhetsky A.V.,Prentki M.,Posner B.I.,Balding D.J.,Meyre D.,Polychronakos C.,Froguel P. .2007 .A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature, 445(7130) : 881-885.

[22] Baptiste-Roberts K.,Barone B.B.,Gary T.L.,Golden S.H.,Wilson L.M.,Bass E.B.,Nicholson W.K. .2009 .Risk factors for type 2 diabetes among women with gestational diabetes: a systematic review. The American Journal of Medicine, 122(3) : 207-214.

[23] Guo Z.,Kasinathan D.,Merriman C.,Nakayama M.,Li H.,Li H.,Xu C.,Wong G.W.,Yu L.,Golson M.L.,Fu D. .2023 .Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies. Diabetes, 72(2) : 184-195.

[24] Siddiqui K.,Nawaz S.S.,Alfadda A.A.,Mujammami M. .2023 .Islet Autoantibodies to Pancreatic Insulin-Producing Beta Cells in Adolescent and Adults with Type 1 Diabetes Mellitus: A CrossSectional Study. Diagnostics, 1736(10) : .

[25] Weijers R.N. .2010 .Three-dimensional structure of β-cellspecific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W. Diabetology & Metabolic Syndrome, 2(1) : 1-8.

[26] Barragán-Álvarez C.P.,Padilla-Camberos E.,Díaz N.F.,Cota-Coronado A.,Hernández-Jiménez C.,Bravo-Reyna C.C.,Díaz-Martínez N.E. .2021 .Loss of Znt8 function in diabetes mellitus: risk or benefit?. Molecular and Cellular Biochemistry, 476(7) : 2703-2718.

[27] Bhattacharya M. .2022 .A brief study of genes vital for diabetes and their relationship. In Contemporary Medical Biotechnology Research for Human Health 41-48, : .

[28] M.J. Daniels M.,Jagielnicki M.,Yeager M. .2020 .Function analysis of human ZnT8 (SLC30A8): A diabetes risk factor and zinc transporter. Current Research in Structural Biology, 2 : 144-155.

[29] Cortez B.N.,Pan H.,Hinthorn S.,Sun H.,Neretti N.,Gloyn A.L.,Aguayo-Mazzucato C. .2024 .Heterogeneity of increased biological age in type 2 diabetes correlates with diferential tissue DNA methylation, biological variables, and pharmacological treatments. GeroScience, 46(2) : 2441-2461.

[30] Horikawa Y.,Miyake K.,Yasuda K.,Enya M.,Hirota Y.,Yamagata K.,Hinokio Y.,Oka Y.,Lwasaki N.,Lwamoto Y.,Yamada Y.,Seino Y.,Maegawa H.,Kashiwagi A.,Yamamoto K.,Tokunaga K.,Takeda J.,Kasuga M. .2008 .Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. The Journal of Clinical Endocrinology & Metabolism, 93(8) : 3136-3141.

[31] Koszarska M.,Strzałkowska N.,Tzvetkov N.T.,Wang D.,Horbańczuk J.O.,Wierzbicka A.,Atanasov A.G.,Jóźwik A. .2023 .-O-glucoside as a Nutrigenomic Factor in Type 2 Diabetes and Its Prominent Impact on Health. International Journal of Molecular Sciences, 9765(11) : .

[32] Kwak S.H.,Srinivasan S.,Chen L.,Todd J.,Mercader J.M.,Jensen E.T.,Divers J.,Mottl A.K.,Pihoker C.,Gandica R.G.,Lafel L.M.,Haymond M.W.,Levitsky L.L.,Pollin T.I.,Florez J.C.,Flannick J. .2024 .Genetic architecture and biology of youth-onset type 2 diabetes. Nature Metabolism, 1(12) : .

[33] J. Zhen Y.,Gu P.,Wang W.,Wang S.,Bian S.,Huang H.,Liang M.,Huang Y.,Yu Q.,Chen G.,Jiang X.,Qui L.,Xiong S.,Liu S. .2024 .Genome-wide association and Mendelian randomisation analysis among 30,699 Chinese pregnant women identifies novel genetic and molecular risk factors for gestational diabetes and glycaemic traits. Diabetologia, 67 : 703-713.

[34] Zhou L.,Zhao J.,Chen B. .2015 .Association between SLC30A8 rs13266634 polymorphism and type 2 diabetes risk: a metaanalysis. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 21 : 2178.

[35] Ericson U.,OrhoMelander M. .2017 .A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8. Genes & Nutrition, 12 : 30.

[36] Syarifuddin S.,Samosir W. .2022 .Characteristics of types of diabetes mellitus II in regional general hospital than rondahaim, simalungun district. Health and Midwife Participation, 3(4) : 144-148.

[37] Akhtar S.,Nasir J.A.,Abbas T.,Sarwar A. .2019 .Diabetes in Pakistan: A systematic review and meta-analysis. Pakistan Journal of Medical Sciences, 1173(4) : .

Citations

Downloads

Views