Meta-analysis of insights into HHEX (rs1111875) and SLC30A8 (rs13266634) gene variants and type 2 diabetes mellitus

Anushka Ray; Animesh Chowdhury; Tushar Barman; Manoj Lama

doi:10.18203/2320-6012.ijrms20263546

Authors

Anushka Ray Department of Zoology, University of Gour Banga, Malda, West Bengal, India https://orcid.org/0009-0006-8381-4043
Animesh Chowdhury Department of Zoology, University of Gour Banga, Malda, West Bengal, India; Department of Zoology, Malda College, Malda, West Bengal, India https://orcid.org/0000-0002-1462-8873
Tushar Barman Department of Zoology, University of Gour Banga, Malda, West Bengal, India https://orcid.org/0009-0005-7766-9225
Manoj Lama Department of Zoology, University of Gour Banga, Malda, West Bengal, India https://orcid.org/0000-0003-3511-5206

DOI:

https://doi.org/10.18203/2320-6012.ijrms20263546

Keywords:

HHEX, SLC30A8, Type 2 diabetes mellitus, Meta-analysis

Abstract

Type 2 diabetes mellitus (T2DM) is aggravated by inherited factors, peripheral insulin resistance and environmental factors. Genome wide association studies (GWAS) revealed more than 400 genetic loci to be associated with T2DM. The function of HHEX gene rs1111875 variant and the insulin secretion response after a glucose load might impact the risk of T2DM mainly via altering pancreatic β-cell activity. The solute carrier family 30, member 8 (SLC30A8) is primarily expressed in pancreatic β-cells and may play a key role in insulin secretory pathway. This current study revealed a significant association between HHEX A>G variant and T2DM in allele (A versus G: p=0.004), Codominant (AA versus GG: p=0.001), Dominant (AA versus AG + GG: p=0.02) and recessive (AA+AG versus GG: p=0.002) inheritance models and for HHEX C>T variant under recessive inheritance model (CC+CT versus TT: p=0.035). In addition, for SLC30A8 C>T variant also associated with T2DM under allele (C versus T: p=0.001), dominant (CC versus CT+TT: p=0.001), recessive (CC+CT versus TT: p=0.001), codominant [(CC versus CT: p=0.007) and (CC versus TT: p≤0.001)] inheritance models. HHEX (rs1111875) and SLC30A8 (rs13266634) gene variants revealed that these gene variants can be a potential factor for etiopathogenesis of T2DM.

References

Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L. The many faces of diabetes: A disease with increasing heterogeneity. The Lancet. 2014;383(9922):1084-94.

Golden SH, Yajnik C, Phatak S, Hanson RL, Knowler WC. Racial/ethnic differences in the burden of type 2 diabetes over the life course: a focus on the USA and India. Diabetologia. 2019;62(10):1751-60.

Aka TD, Saha U, Shati SA, Aziz MA, Begum M, Hussain MS, et al. Risk of type 2 diabetes mellitus and cardiovascular complications in KCNJ11, HHEX and SLC30A8 genetic polymorphisms carriers: A case-control study. Heliyon. 2021;7(11).

Tremblay J, Haloui M, Attaoua R, Tahir R, Hishmih C, Harvey F, et al. Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control. Diabetologia. 2021;64(9):2012-25.

Li YY, Lu XZ, Wang H, Yang XX, Geng HY, Gong G, et al. Solute carrier family 30 member 8 gene 807C/T polymorphism and type 2 diabetes mellitus in the Chinese population: A meta-analysis including 6,942 subjects. Front Endocrinol. 2018;9:6.

Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41-7.

Krentz NAJ, Gloyn AL. Insights into pancreatic islet cell dysfunction from type 2 diabetes mellitus genetics. Nat Rev Endocrinol. 2020;16(4):202-12.

Sheikhpour M, Abolfathi H, Khatami S, Meshkani R, Barghi TS. The interaction between gene profile and obesity in type 2 diabetes: A review. Obes Med. 2020;18:100197.

Bhowmick A, Sarkar P, Baruah MP, Bodhini D, Radha V, Mohan V, et al. Association of SLC30A8, CDKAL1, TCF7L2 and HHEX Gene Polymorphisms with Type 2 Diabetes in the Population of North East India. Cytol Genet. 2020;54(2):165-72.

Goyal Y, Verma AK, Kumar S, Bhatt D, Ahmad F, Dev K. Association of SLC30A8 (rs13266634) and GLIS3 (rs7034200) gene variant in development of type 2 diabetes mellitus in Indian population: A case-control study. Gene Rep. 2022;28.

Lu CC, Chen YT, Chen SY, Hsu YM, Lin CC, Tsao JW, et al. Hematopoietically expressed homeobox gene is associated with type 2 diabetes in KK Cg-Ay/J mice and a Taiwanese han Chinese population. Exp Ther Med. 2018;16(1):185-91.

Xu P, Che Y, Cao Y, Wu X, Sun H, Liang F, et al. Polymorphisms of TCF7L2 and HHEX genes in Chinese women with polycystic ovary syndrome. J Assist Reprod Genet. 2010;27(1):23-8.

Galavi H, Mollashahee-Kohkan F, Saravani R, Sargazi S, Noorzehi N, Shahraki H. HHEX gene polymorphisms and type 2 diabetes mellitus: A case-control report from Iran. J Cell Biochem. 2019;120(10):16445-51.

Weijers RN. Three-dimensional structure of β-cell-specific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W. Diabetol Metab Syndr. 2010;2(1):33.

Syring KE, Boortz KA, Oeser JK, Ustione A, Platt KA, Shadoan MK, et al. Combined deletion of Slc30a7 and Slc30a8 unmasks a critical role for ZnT8 in glucose-stimulated insulin secretion. Endocrinology. 2016;157(12):4534-41.

Murgia C, Devirgiliis C, Mancini E, Donadel G, Zalewski P, Perozzi G. Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed by distinct rodent endocrine cell types in the pancreas and other glands. Nutr Metab Cardiovasc Dis. 2009;19(6):431-9.

Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, et al. A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants. Science. 2007;316(5829):1341-5.

Xiang J, Li XY, Xu M, Hong J, Huang Y, Tan JR, et al. Zinc transporter-8 gene (SLC30A8) is associated with type 2 diabetes in Chinese. J Clin Endocrinol Metab. 2008;93(10):4107-12.

Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009:19621072.

Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58.

Grant J, Hunter A. Measuring inconsistency in knowledgebases. J Intell Inf Syst. 2006;27(2):159-84.

Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Br Med J. 1997;315(7109):629-34.

Furukawa Y, Shimada T, Furuta H, Matsuno S, Kusuyama A, Doi A, et al. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2008;93(1):310-4.

Kommoju UJ, Maruda J, Kadarkarai S, Irgam K, Kotla JP, Velaga L, et al. No detectable association of IGF2BP2 and SLC30A8 genes with type 2 diabetes in the population of Hyderabad, India. Meta Gene. 2013;1:15-23.

Khodyrev DS, Nikitin AG, Brovkin AN, Lavrikova EY, Lebedeva NO, Vikulova OK, et al. The analysis of association between type 2 diabetes and polymorphic markers in the CDKAL1 gene and in the HHEX/IDE locus. Russ J Genet. 2016;52(11):1192-9.

Plengvidhya N, Chanprasert C, Chongjaroen N, Yenchitsomanus P, Homsanit M, Tangjittipokin W. Impact of KCNQ1, CDKN2A/2B, CDKAL1, HHEX, MTNR1B, SLC30A8, TCF7L2, and UBE2E2 on risk of developing type 2 diabetes in Thai population. BMC Med Genet. 2018;19(1):93.

Verma AK, Goyal Y, Bhatt D, Beg MMA, Dev K, Alsahli MA, et al. Association between cdkal1, hhex, cdkn2a/2b and igf2bp2 gene polymorphisms and susceptibility to type 2 diabetes in Uttarakhand, India. Diabetes Metab Syndr Obes. 2021;14:23-36.

Li C, Shen K, Yang M, Yang Y, Tao W, He S, et al. Association between single nucleotide polymorphisms in cdkal1 and hhex and type 2 diabetes in chinese population. Diabetes Metab Syndr Obes. 2020;13:5113-23.

Schulze MB, Al-Hasani H, Boeing H, Fisher E, Döring F, Joost HG. Variation in the HHEX-IDE gene region predisposes to type 2 diabetes in the prospective, population-based EPIC-Potsdam cohort. Diabetologia. 2007;50(11):2405-7.

Vliet-Ostaptchouk J v van, Onland-Moret NC, van Haeften TW, Franke L, Elbers CC, Shiri-Sverdlov R, et al. HHEX gene polymorphisms are associated with type 2 diabetes in the Dutch Breda cohort. Eur J Hum Genet. 2008;16(5):652-6.

Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K, et al. Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab. 2008;93(8):3136-41.

Tabara Y, Osawa H, Kawamoto R, Onuma H, Shimizu I, Miki T, et al. Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes. 2009;58(2):493-8.

Zhou DZ, Liu Y, Zhang D, Liu SM, Yu L, Yang YF, et al. Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese. J Hum Genet. 2010;55(12):810-5.

Sun R, Liu JP, Gao C, Xiong YY, Li M, Wang YP, et al. Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population. Oncotarget. 2016;7(20):29770-9.

Cauchi S, Proença C, Choquet H, Gaget S, De Graeve F, Marre M, et al. Analysis of novel risk loci for type 2 diabetes in a general French population: The D.E.S.I.R. study. J Mol Med. 2008;86(3):341-8.

Pivovarova O, Nikiforova VJ, Pfeiffer AFH, Rudovich N. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. Diabetes Metab Res Rev. 2009;25(2):156-62.

Shaker NQ, Ali SK. Obesity-Related Type 2 Diabetes Mellitus and HHEX Gene rs1111875 C/T Polymorphisms in Iraqi Population. J Kufa Chem Sci. 2023;3(1):274-87.

Rong R, Hanson RL, Ortiz D, Wiedrich C, Kobes S, Knowler WC, et al. Association analysis of variation in/near FT0, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in pima indians. Diabetes. 2009;58(2):478-88.

Gutiérrez-Vidal R, Rodríguez-Trejo A, Canizales-Quinteros S, Herrera-Cornejo M, Granados-Silvestre MA, Montúfar-Robles I, et al. LOC387761 polymorphism is associated with type 2 diabetes in the Mexican population. Genet Test Mol Biomark. 2011;15(1–2):79-83.

Horikoshi M, Hara K, Ito C, Shojima N, Nagai R, Ueki K, et al. Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia. 2007;50(12):2461-6.

Abu Seman N, Wan Mohamud WN, Östenson CG, Brismar K, Gu HF. Increased dna methylation of the slc30a8 gene promoter is associated with type 2 diabetes in a malay population. Clin Epigenet. 2015;7(1):7-30.

Zheng X, Ren W, Zhang S, Liu J, Li S, Li J, et al. Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population. Mol Biol Rep. 2012;39(1):17-23.

Lee YH, Kang ES, Kim SH, Han SJ, Kim CH, Kim HJ, et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53(11–12):991-8.

Plengvidhya N, Chanprasert C, Chongjaroen N, Yenchitsomanus P, Homsanit M, Tangjittipokin W. Impact of KCNQ1, CDKN2A/2B, CDKAL1, HHEX, MTNR1B, SLC30A8, TCF7L2, and UBE2E2 on risk of developing type 2 diabetes in Thai population. BMC Med Genet. 2018;19(1).

Ng MCY, Park KS, Oh B, Tam CHT, Cho YM, Shin HD, et al. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes. 2008;57(8):2226-33.

Kommoju UJ, Samy SK, Maruda J, Irgam K, Kotla JP, Velaga L, et al. Association of CDKAL1, CDKN2A/B & HHEX gene olymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India. Indian J Med Res. 2016;143:455-63.

Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007;39(6):770-5.

Wu Y, Li H, Loos RJF, Yu Z, Ye X, Chen L, et al. Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population. Diabetes. 2008;57(10):2834-42.

Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, Kaku K, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008;57(3):791-5.

Salem SD, Saif-Ali R, Ismail IS, Al-Hamodi Z, Muniandy S. Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study. BMC Endocr Disord. 2014;14(2).

Alikhan I, Poornima S, Jahan P, Rao P, Hasan Q. Type 2 diabetes mellitus and the association of candidate genes in asian indian population from Hyderabad, India. J Clin Diagn Res. 2015;9(11):GC01-5.

Wang Y, Qiao W, Zhao X, Tao M. Quantitative assessment of the influence of hematopoietically expressed homeobox variant (rs1111875) on type 2 diabetes risk. Mol Genet Metab. 2011;102(2):194-9.

Rong YA, Fan X, Ming LH, Wen XH, Chun WX. Association between SLC30A8 gene polymorphisms and diabetes mellitus after renal transplantation. Chin J Tissue Eng Res. 2013;17(31):5613.

Liu Y, Wang Z, Chi Z, Wang T. Research on correlation between rs13266634 C/T SNP of SLC 30A 8 gene and susceptibility to type 2 diabetes mellitus. J Chin Med Univ. 2015;44:494-7.

Su Y, Ma Y, Yao H, Zhu Z, Wang T, Wang Z, et al. Association between polymorphisms of SLC30A8 and their interaction and type 2 diabetes in Uyhgur nationality. Chin J Diab. 2016;24:12-6.

Zhong K, Chang X. TCF7L2 and SLC30A8 Gene Polymorphisms Preliminary Study of Type 2 Diabetes Mellitus in Xinjiang Kazak Population. A Dissertation of Shihezi University; 2013.

Zhang S, Liu J, Guo L, Ma X, Liu J. Association of SLC30A8 gene rs13266634 polymorphism in with type 2 diabetes in Gansu Chinese Han and Hui population. Chin J Gerontol. 2015;35:898-900.

Sarkar P, Bhowmick A, Baruah M, Bhattacharjee S, Subhadra P, Banu S. Determination of individual type 2 diabetes risk profile in the North East Indian population & its association with anthropometric parameters. Indian J Med Res. 2019;150(4):390-8.

Phani NM, Adhikari P, Nagri SK, D’Souza SC, Satyamoorthy K, Rai PS. Replication and relevance of multiple susceptibility loci discovered from genome wide association studies for type 2 diabetes in an Indian population. PLoS One. 2016;11(6).

Ali SS, Bahadar H, Shah H, Ali S, Khan M, Khuda F, et al. Screening of Type 2 Diabetes Mellitus Patients of Khyber Pakhtunkhwa for SLC30A8 (rs13266634) Variant Associated with Disease Susceptibility. Pak Biomed J. 2024;7(3):55-61.

Sanghera DK, Ortega L, Han S, Singh J, Ralhan SK, Wander GS, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet. 2008;9.

Lin Y, Li P, Cai L, Zhang B, Tang X, Zhang X, et al. Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population. BMC Med Genet. 2010;97.

Zhang S, Liu J, Liu J, Wei S. Association of SLC30A8 gene rs13266634 polymorphism in with type 2 diabetes in Chinese Dongxiang population. Gansu Sci Technol. 2014;30:138-9.

Wang Z, Zhang S, Wang Z, Gong L, Li R, Ren W, et al. Relationship of rs13266634 polymorphism in SLC30A8 (solute carrier family30, member 8) gene with type 2 diabetes in Chinese Han population. Shanghai Med J. 2008;31:323-7.

Li X, Su Y, Yan Z, Zhang J, Gu L, Qin W, et al. Association of rs13266634 polymorphism in SLC30A8 gene with type 2 diabetes in Han Population of Inner Mongolia. Prog Mod Biomed. 2011;11:2221-3.

Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881-5.

Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes. Science. 2007;316(5829):1336-41.

Cauchi S, Meyre D, Durand E, Proença C, Marre M, Hadjadj S, et al. Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value. PLoS One. 2008;3(5).

Cauchi S, Nead KT, Choquet H, Horber F, Potoczna N, Balkau B, et al. The genetic susceptibility to type 2 diabetes may be modulated by obesity status: Implications for association studies. BMC Med Genet. 2008;9.

Bazzi MD, Nasr FA, Alanazi MS, Alamri A, Turjoman AA, Moustafa AS, et al. Association between FTO, MC4R, SLC30A8, and KCNQ1 gene variants and type 2 diabetes in Saudi population. Genet Mol Res. 2014;13(4):10194-203.

Sharif FA, Shubair ME, Zaharna MM, Ashour MJ, Altalalgah IO, Najjar M, et al. Genetic Polymorphism and Risk of having Type 2 Diabetes in a Palestinian Population: A Study of 16 Gene Polymorphisms. Adv Diabetes Endocrinol. 2018;3(1):6.

Mashal S, Khanfar M, Al-Khalayfa S, Srour L, Mustafa L, Hakooz NM, et al. SLC30A8 gene polymorphism rs13266634 associated with increased risk for developing type 2 diabetes mellitus in Jordanian population. Gene. 2021;768.

Soltanian AR, Hosseini B, Mahjub H, Bahreini F, Ghaffari ME. A Bayesian analysis for investigating the association between rs13266634 polymorphism in SLC30A8 gene and type 2 diabetes. J Diabetes Metab Disord. 2020;19(1):337-42.

Yazdi KV, Kalantar SM, Houshmand M, Rahmanian M, Manaviat MR, Jahani MR, et al. Slc30a8, cdkal1, tcf7l2, kcnq1 and igf2bp2 are associated with type 2 diabetes mellitus in iranian patients. Diabetes Metab Syndr Obes. 2020;13:897-906.

Potapov VA, Chistiakov DA, Shamkhalova MS, Shestakova MV, Nosikov VV. TCF7L2 rs12255372 and SLC30A8 rs13266634 confer susceptibility to type 2 diabetes in a Russian population. Diabetes Metab Syndr Clin Res Rev. 2009;3(4):219-23.

Nikitin AG, Potapov VY, Brovkina OI, Koksharova EO, Khodyrev DS, Philippov YI, et al. Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population. PeerJ. 2017;2017(7).

Aişeoğlu B, Parmaksız A, Sevimli UD. Investigation Of Slc30a8 (Rs13266634) Gene Polymorphisms In Type 2 Diabetes Mellitus Patients. Eurasian Mol Biochem Sci. 2023;2(2):6-13.

Banihashemi P, Aghaei Meybodi HR, Afshari M, Sarhangi N, Hasanzad M. Association analysis of HHEX gene variant with type 2 diabetes risk. Int J Diabetes Dev Ctries. 2020;41(1):43-7.

Jan A, Zakiullah, Khuda F, Akbar R. Validation of Genome-Wide Association Studies (GWAS)-ldentified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population. J ASEAN Fed Endocr Soc. 2022;37:S1.

Huang Q, Yin JY, Dai XP, Wu J, Chen X, Deng CS, et al. Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients. Eur J Clin Pharmacol. 2010;66(12):1207-15.

Mohaddes SM, Karami F, Gharesouran J, Bahrami A. The Soluble Carrier 30 A8 (SLC30A8) Gene Polymorphism and Risk of Diabetes Mellitus Type 2 in Eastern Azerbijan Population of Iran. J Sci Islam Repub Iran. 2012;23(1):15-20.

Faghih H, Khatami SR, Azarpira N, Foroughmand AM. SLC30A8 gene polymorphism (rs13266634 C/T) and type 2 diabetes mellitus in south Iranian population. Mol Biol Rep. 2014;41(5):2709-15.

Sargazi S, Heidari Nia M, Sargazi FM, Sheervalilou R, Saravani R, Mirinejad S. SNPs in the 3′-untranslated region of SLC30A8 confer risk of type 2 diabetes mellitus in a south-east Iranian population: Evidences from case-control and bioinformatics studies. J Diabetes Metab Disord. 2020;19(2):979-88.

Alharbi KK, Abudawood M, Ali Khan I. Amino-acid amendment of Arginine-325-Tryptophan in rs13266634 genetic polymorphism studies of the SLC30A8 gene with type 2 diabetes-mellitus patients featuring a positive family history in the Saudi population. J King Saud Univ Sci. 2021;33(1).

Mitu FS, Hossain MM, Das SC, Islam MM, Barman DN, Das Gupta S. Association of SLC30A8 rs13266634 gene polymorphism with type 2 diabetes mellitus (T2DM) in a population of Noakhali, Bangladesh: a case–control study. Egypt J Med Hum Genet. 2024;25(1).

Almawi WY, Nemr R, Keleshian SH, Echtay A, Saldanha FL, AlDoseri FA, et al. A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population. Diabetes Res Clin Pract. 2013;102(2):117-22.

Muneam HAA, Alzubaidy HFS, Alwaidh RH. Explore The Effect of SLC30A8 Gene on Lipid Profile and Anthropometric Parameters in T2DM Patients In AL-Najaf Population. HIV Nurs. 2023;23(3):175-80.

Boutsouris K, Poumpouridou N, Katsarou M, Gourzi SF, Tentolouris K, Liapi C, et al. Frequency distribution of TCF7l2, MTNR1B, CDKAl1, SLC30A8 and FTO gene polymorphisms predisposing to type II diabetes mellitus and/or obesity in a greek population and their impact in personalized medicine. Arch Balk Med Union. 2016;51:157-63.

Chen Y, Wang X, Zhao Y, Shi X, Wang Y. Association of SLC30A8 (rs13266634), CDKN2A/2B (rs10811661) and TCF7L2 (rs7903146) with theinsulin resistance in type 2 diabetes in ChineseHan population in Northeast part of China. Int J Clin Exp Pathol. 2017;10(3):3830-6.

Han X, Luo Y, Ren Q, Zhang X, Wang F, Sun X, et al. Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in Type 2 Diabetes in a Chinese population. BMC Med Genet. 2010;11:81.

Goyal Y, Verma AK, Joshi PC, Dev K. Contemplating the role of genetic variants of HHEX, CDKAL1, WFS1 and SLC30A8 genes of TYPE-2 diabetes in Asians ethnic groups. Gene Rep. 2019;17.

Herder C, Rathmann W, Strassburger K, Finner H, Grallert H, Huth C, et al. Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type 2 diabetes independently of BMI in the German KORA studies. Horm Metab Res. 2008;40(10):722-6.

Nordman S, Östenson CG, Efendic S, Gu HF. Loci of TCF7L2, HHEX and IDE on chromosome 10q and the susceptibility of their genetic polymorphisms to type 2 diabetes. Exp Clin Endocrinol Diabetes. 2009;117(4):186-90.

Andersson EA, Pilgaard K, Pisinger C, Harder MN, Grarup N, Færch K, et al. Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight. Diabetologia. 2010;53(9):1908-16.

Gupta V, Khadgawat R, Tony NG HK, Kumar S, Aggarwal A, Rao VR, et al. A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of North India. Ann Hum Genet. 2010;74(4):361-8.

Turki A, Al-Zaben GS, Khirallah M, Marmouch H, Mahjoub T, Almawi WY. Gender-dependent associations of CDKN2A/2B, KCNJ11, POLI, SLC30A8, and TCF7L2 variants with type 2 diabetes in (North African) Tunisian Arabs. Diabetes Res Clin Pract. 2014;103(3).

Lara-Riegos JC, Ortiz-López MG, Peña-Espinoza BI, Montúfar-Robles I, Peña-Rico MA, Sánchez-Pozos K, et al. Diabetes susceptibility in Mayas: Evidence for the involvement of polymorphisms in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes. Gene. 2015;565(1):68-75.

Lin Z, Wang Y, Zhang B, Jin Z. Association of type 2 diabetes susceptible genes GCKR, SLC30A8, and FTO polymorphisms with gestational diabetes mellitus risk: a meta-analysis. Endocrine. 2018;62(1):34-45.

Awadallah EA, Hasan NS, Awad MAM, Kamel SA, Yousef RN, Musa NI, et al. Associations of GCKR, TCF7L2, SLC30A8 and IGFB Polymorphisms with Type 2 Diabetes Mellitus in Egyptian Populations. Jordan J Biol Sci. 2020;8:3.

Staiger H, Machicao F, Stefan N, Tschritter O, Thamer C, Kantartzis K, et al. Polymorphisms within novel risk loci for type 2 diabetes determine β-cell function. PLoS One. 2007;2(9).

Liju S, Chidambaram M, Mohan V, Radha V. Impact of type 2 diabetes variants identified through genome-wide association studies in early-onset type 2 diabetes from South Indian population. Genomics Inform. 2020;18(3):1-12.

Fan M, Li W, Wang L, Gu S, Dong S, Chen M, et al. Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis. Endocrine. 2016;53(2):381-94.