Personalized and Precision Medicine Journal
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Vitamin D Binding Protein Gene Polymorphisms and its Association with Type 2 Diabetes Mellitus in an Iranian Population

Document Type : Original Article

Authors

Heidar Aziznejad 1
Ares Alizadeh 2
Marva Aziznejad 3
Zahra Sanjideh 4
Parisa Maziri 5

1 The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran

2 Van Yuzuncu Yil University, Faculty of Medicine, Department of Internal Medicine, Department of Pharmacology, Zeve Campus, 65080 Tusba / VAN, Turkey..

3 Department of Basic Sciences , Faculty of veterinary medicine, Urmia University, Urmia, Iran

4 The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran.

5 Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran

https://doi.org/10.22034/pmj.2023.702082
Abstract
Polymorphisms of Vitamin D-binding protein (DBP) may represent a risk factor for susceptibility to Type 2 Diabetes Mellitus (T2DM). Two polymorphisms are common at codons 420 (ACG to AAG) and 416 (GAT to GAG) in the DBP gene. The present study aimed to assess variants of DBP at codons 420 and 416 utilizing polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), which were digested by Sty I (codon 420) and Hae III (codon 416) restriction enzyme. For this purpose, 240 patients were recruited along with 159 controls. The genotype frequency of Glu/Glu at codon 416 in control and patient groups was 25.16% and 32.92% respectively. Moreover, the genotype frequency of Lys/Lys was 6.67% in patients and 1.89% in controls at codon 420. A significant difference was found between control and patient groups in genotype frequencies at codon 420 (p<0.05). It was found that there might be an association between the vitamin D-binding protein gene and T2DM. 

Keywords

Type 2 Diabetes Mellitus
Vitamin D Binding Protein Gene Polymorphisms
PCR-RFLP
1.Alberti, K.G.M.M. and Zimmet, P.Z.,. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabetic medicine;1998 15, 539-553.
2.World Health Organization,. Global report on diabetes. World Health Organization, Geneva;2016.
3.Zimmet, P., Alberti, K. and Shaw, J.,. Global and societal implications of the diabetes epidemic. Nature;2001 414, 782-787.
4.Song C, Gong W, Ding C, Wang R, Fang H, Liu A. Gene-Environment Interaction on Type 2 Diabetes Risk among Chinese Adults Born in Early 1960s. Genes (Basel). 2022 Apr 5;13(4):645. 
5.Battini Mohan Reddy*, Rayabarapu Pranavchand And S A A Latheef, Overview of genomics and post-genomics research on type 2 diabetes mellitus: Future perspectives and a framework for further studies. J Biosci ;2019: 44:21.
6.Baz-Hecht, M. and Goldfine, A.B., The impact of vitamin D deficiency on diabetes and cardiovascular risk. Current Opinion in Endocrinology, Diabetes and Obesity 2010;17, 113-119.
7.El Baba, K., Zantout, M.S., Akel, R. and Azar, S.T. Seasonal variation of vitamin D and HbA1c levels in patients with type 1 diabetes mellitus in the Middle East. International journal of general medicine 2011; 4, 635.
8.Nasr MH, Hassan BAR, Othman N, Karuppannan M, Abdulaziz N, Mohammed AH, Alsarani MA, Eskembaji MH, Aman AM, Othman G. Prevalence of Vitamin D Deficiency Between Type 2 Diabetes Mellitus Patients and Non-Diabetics in the Arab Gulf. Diabetes Metab Syndr Obes. 2022;15:647-657
9.Khudayar M, Nadeem A, Lodi MN, Rehman K, Jawaid SI, Mehboob A, Aleem AS, Mirza REF, Ahmed M, Abbas K. The Association Between Deficiency of Vitamin D and Diabetes Mellitus Type 2 (DMT2). Cureus. 2022 Feb 14;14(2):e22221. 
10. Norman, A. The vitamin D endocrine system: identification of another piece of the puzzle. Endocrinology1994; 134, 1601A-1601C.
11. Al Ghadeer HA, AlRamadan MS, Al Amer MM, Alshawaf MJ, Alali FJ, Bubshait AA, Alramadhan MA, Almurayhil Z, Aldandan NS, AlKhamis MA, AlHaddad HA, AlOmair A. Vitamin D Serum Levels in Type 2 Diabetic Patients: A Cross-Sectional Study. Cureus. 2022 Feb 24;14(2):e22558.
12. Erasmus R, Maepa S, Machingura I, Davids S, Raghubeer S, Matsha T. Vitamin D, Vitamin D-Binding Proteins, and VDR Polymorphisms in Individuals with Hyperglycaemia. Nutrients. 2022 Jul 30;14(15):3147.
13.Boucher, B., Mannan, N., Noonan, K., Hales, C. and Evans, S., 1995. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia1; 38, 1239-1245
14.Zhang TP, Chen SS, Zhang GY, Shi SJ, Wei L, Li HM. Association of vitamin D pathway genes polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population. Genes & nutrition. 2021 Dec;16(1):1-2.
15.Dai32ger, S.P., Schanfield, M.S. and Cavalli-Sforza, L. Group-specific component (Gc) proteins bind vitamin D and 25-hydroxyvitamin D. Proceedings of the National Academy of Sciences1975, 72, 2076-2080.
16.Hirai, M., Suzuki, S., Hinokio, Y., Chiba, M., Kasuga, S., Hirai, A. and Toyota, T.,. Group specific component protein genotype is associated with NIDDM in Japan. Diabetologia1998; 41, 742-743.
17.Wang, T.J., Zhang, F., Richards, J.B., Kestenbaum, B., Van Meurs, J.B., Berry, D., Kiel, D.P., Streeten, E.A., Ohlsson, C. and Koller, D.L. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. The Lancet 2010; 376, 180-188.
18.Klupa, T., Malecki, M., Hanna, L., Sieradzka, J., Frey, J., Warram, J.H., Sieradzki, J. and Krolewski, A.S. Amino acid variants of the vitamin D-binding protein and risk of diabetes in white Americans of European origin. European journal of endocrinology 1999;141, 490-493.
19.Jorde, R.. The role of vitamin D binding protein, total and free 25-hydroxyvitamin D in diabetes. Frontiers in endocrinology2019; 10, 79.
20.Braun, A., Kofler, A., Morawietz, S. and Cleve, H.,. Sequence and organization of the human vitamin D-binding protein gene. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression1993; 1216, 385-394
21.Speeckaert, M., Huang, G., Delanghe, J.R. and Taes, Y.E.,. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clinica chimica2006 acta 372, 33-42.
22.Chen, H., Zhang, L., He, Z., Zhong, X., Zhang, J., Li, M. and Bai, J.,. Vitamin D binding protein gene polymorphisms and chronic obstructive pulmonary disease: a meta-analysis. Journal of thoracic disease2015; 7, 1423
23.Baier, L.J., Dobberfuhl, A.M., Pratley, R.E., Hanson, R.L. and Bogardus, C.,. Variations in the vitamin D-binding protein (Gc locus) are associated with oral glucose tolerance in nondiabetic Pima Indians. The journal of clinical endocrinology & metabolism1998; 83, 2993-2996.
24.Seshadri, K.G., Tamilselvan, B. and Rajendran, A.,. Role of vitamin D in diabetes. Journal of Endocrinology and Metabolism2011, 1, 47-56.
25.Kayaniyil, S., Vieth, R., Retnakaran, R., Knight, J.A., Qi, Y., Gerstein, H.C., Perkins, B.A., Harris, S.B., Zinman, B. and Hanley, A.J.,. Association of vitamin D with insulin resistance and β-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes care2010; 33, 1379-1381.
26.Hirai, M., Suzuki, S., Hinokio, Y., Hirai, A., Chiba, M., Akai, H., Suzuki, C. and Toyota, T.,. Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance. The Journal of clinical endocrinology & metabolism2000 85, 1951-1953.
27.Wang, Y., Yu, Y., Li, Z., Li, J., Wang, C. and Wang, H.,. Correlation between polymorphism of vitamin D binding protein gene and type 2 diabetes mellitus in Han people of Shanghai. Chin J Endocrinol Metab2006 22, 263-4.
28.Shao, X., Miao, H., Jiang, X. and Wei, Y.,. Association of vitamin D binding protein receptor gene polymorphism and risk of type 2 diabetes mellitus in Han people of Nanjing Province. Chin J Mod Med2012; 22, 45-8.
 29.Malecki, M.T., Klupa, T., Wanic, K., Cyganek, K., Frey, J. and Sieradzki, J.,. Vitamin D binding protein gene and genetic susceptibility to type 2 diabetes mellitus in a Polish population. Diabetes research and clinical practice2002; 57, 99-104.
30.Ye, W.-Z., Dubois-Laforgue, D., Bellanné-Chantelot, C., Timsit, J. and Velho, G.,. Variations in the vitamin D-binding protein (Gc locus) and risk of type 2 diabetes mellitus in French Caucasians. Metabolism-Clinical and Experimental 2001;50, 366-369.
31.Wang, G., Li, Y., Li, L., Yu, F., Cui, L., Ba, Y., Li, W. and Wang, C. Association of the vitamin D binding protein polymorphisms with the risk of type 2 diabetes mellitus: a meta-analysis. BMJ open2014; 4, e005617.
32. Rahman, M.M., Hosen, M.B., Faruk, M.O., Hasan, M.M., Kabir, Y. and Howlader, M.Z.H. Association of vitamin D and vitamin D binding protein (DBP) gene polymorphism with susceptibility of type 2 diabetes mellitus in Bangladesh. Gene2017; 636, 42-47.
33.Wu, Y., Ding, Y., Tanaka, Y. and Zhang, W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. International journal of medical sciences 2014; 11, 1185.
Personalized and Precision Medicine Journal
Volume 8, Issue 28 - Serial Number 28
Original article
Winter 2023
Pages 20-25

  • Receive Date 11 November 2022
  • Revise Date 01 February 2023
  • Accept Date 01 March 2023

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