Association of Common Single-nucleotide Polymorphism of HHEX with Type 2 Diabetes Mellitus

Overview

Journal J Diabetes Metab Disord

Specialty Endocrinology

Date 2024 Jun 27

PMID 38932910

Authors

Saeedeh Hasti

Mani Mirfeizi

Mahdi Afshari

Mandana Hasanzad

Farhad Adhami Moghadam

Hamid Reza Aghaei Meybodi

Affiliations

Soon will be listed here.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that occurs as a result of insulin resistance and low insulin production. T2DM involves many organ systems that include macro-vascular and micro-vascular complications. Several genome-wide association studies (GWAS) and candidate gene studies have suggested a large number of single nucleotide polymorphisms (SNPs) on several genes such as that were associated with T2DM susceptibility. The current study aims to look at the relationship between the risk of T2DM and the HHEX gene variant rs7923837.

Methods: In this case-control study genotyping of rs7923837 of the gene was performed using the PCR-RFLP and Sanger sequencing method.

Results: Frequencies of GG genotype of rs7923837 polymorphism of among subjects with and without diabetes mellitus were 33.77% and 25.47% respectively. Corresponding prevalence for the AG genotype was 51.08% and 64.15% among subjects with and without diabetes mellitus respectively. The differences were not statistically significant ( = 0.08).

Conclusion: Our study revealed that polymorphisms rs7923837 of were not associated with T2DM.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01407-5.

References

Pivovarova O, Nikiforova V, Pfeiffer A, 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. DOI: 10.1002/dmrr.926. View

Pal A, McCarthy M . The genetics of type 2 diabetes and its clinical relevance. Clin Genet. 2012; 83(4):297-306. DOI: 10.1111/cge.12055. View

Bort R, Martinez-Barbera J, Beddington R, Zaret K . Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development. 2004; 131(4):797-806. DOI: 10.1242/dev.00965. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Rhodes C, White M . Molecular insights into insulin action and secretion. Eur J Clin Invest. 2002; 32 Suppl 3:3-13. DOI: 10.1046/j.1365-2362.32.s3.2.x. View

van Vliet-Ostaptchouk J, Onland-Moret N, van Haeften T, Franke L, Elbers C, Shiri-Sverdlov R . HHEX gene polymorphisms are associated with type 2 diabetes in the Dutch Breda cohort. Eur J Hum Genet. 2008; 16(5):652-6. DOI: 10.1038/sj.ejhg.5202008. View

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan B . IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2021; 183:109119. PMC: 11057359. DOI: 10.1016/j.diabres.2021.109119. View

Egi M, Bellomo R, Stachowski E, French C, Hart G . Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006; 105(2):244-52. DOI: 10.1097/00000542-200608000-00006. View

Hunter M, Wilson C, Jiang X, Cong R, Vasavada H, Kaestner K . The homeobox gene Hhex is essential for proper hepatoblast differentiation and bile duct morphogenesis. Dev Biol. 2007; 308(2):355-67. PMC: 2045067. DOI: 10.1016/j.ydbio.2007.05.028. View

10.

Furukawa Y, Shimada T, Furuta H, Matsuno S, Kusuyama A, Doi A . Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2007; 93(1):310-4. DOI: 10.1210/jc.2007-1029. View

11.

Ferrannini E, Gastaldelli A, Iozzo P . Pathophysiology of prediabetes. Med Clin North Am. 2011; 95(2):327-39, vii-viii. DOI: 10.1016/j.mcna.2010.11.005. View

12.

Qian Y, Lu F, Dong M, Lin Y, Li H, Chen J . Genetic variants of IDE-KIF11-HHEX at 10q23.33 associated with type 2 diabetes risk: a fine-mapping study in Chinese population. PLoS One. 2012; 7(4):e35060. PMC: 3323633. DOI: 10.1371/journal.pone.0035060. View

13.

Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C . Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes. 2002; 51(5):1437-42. DOI: 10.2337/diabetes.51.5.1437. View

14.

Donath M, Ehses J, Maedler K, Schumann D, Ellingsgaard H, Eppler E . Mechanisms of beta-cell death in type 2 diabetes. Diabetes. 2005; 54 Suppl 2:S108-13. DOI: 10.2337/diabetes.54.suppl_2.s108. View

15.

Shojima N, Yamauchi T . Progress in genetics of type 2 diabetes and diabetic complications. J Diabetes Investig. 2023; 14(4):503-515. PMC: 10034958. DOI: 10.1111/jdi.13970. View

16.

Marathe P, Gao H, Close K . American Diabetes Association Standards of Medical Care in Diabetes 2017. J Diabetes. 2017; 9(4):320-324. DOI: 10.1111/1753-0407.12524. View

17.

Chang Y, Liu P, Yu Y, Kuo S, Chang T, Jiang Y . Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. PLoS One. 2014; 9(4):e95045. PMC: 3988150. DOI: 10.1371/journal.pone.0095045. View

18.

Ali O . Genetics of type 2 diabetes. World J Diabetes. 2013; 4(4):114-23. PMC: 3746083. DOI: 10.4239/wjd.v4.i4.114. View

19.

Cai Y, Yi J, Ma Y, Fu D . Meta-analysis of the effect of HHEX gene polymorphism on the risk of type 2 diabetes. Mutagenesis. 2010; 26(2):309-14. DOI: 10.1093/mutage/geq095. View

20.

Li X, Li Y, Song B, Guo S, Chu S, Jia N . Hematopoietically-expressed homeobox gene three widely-evaluated polymorphisms and risk for diabetes: a meta-analysis. PLoS One. 2012; 7(11):e49917. PMC: 3499530. DOI: 10.1371/journal.pone.0049917. View