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Zinc (Zn), an essential mineral for the organism, it has functions in carbohydrate, protein, lipid, nucleic acid, heme synthesis, gene expression, reproduction and embryogenesis. In zinc deficiency, clinical findings such as growth and development retardation, hypogonadism, hepatosplenomegaly, delayed wound healing, congenital anomalies, increased susceptibility to infections, impaired neurophysiological performance and impaired sense of smell and taste occur (Belgemen, T., & Nejat, A. K. A. R., 2004). The main food sources for zinc are red meat, chicken, fish, seafood, oilseeds, legumes, grains and dairy products. Roles such as regulating the absorption of Zn from the intestines and storing or releasing Zn within the cell are performed by proteins called metallothioneins (Gizlici, M. N., & Çatak, J. 2019).

Zinc and IL-6 Gene Relationship

Interleukin-6 (IL6) is a cell signalling molecule associated with more than 20 diseases, including inflammatory, neurological, vascular, and malignant processes, and the most studied single nucleotide polymorphism (SNP) in the IL6 gene is rs1800795 (−174G < C). This SNP is located in the promoter region and the C allele has been associated with increases or decreases in IL6 levels in various tissues (Khankhanian, P. et al., 2013).

Zinc and SLC30A8 Gene Relationship

The SLC30A8 gene encodes ZnT8, and its expression is largely restricted to beta and, to a lesser extent, alpha cells of the pancreas (Rutter GA and Chimienti F., 2015). ZnT8 is a transmembrane protein belonging to the family of zinc transporters, involved in the transport of zinc ions produced from the cytoplasm to insulin vesicles and plays an important role in insulin maturation (Thirunavukkarasu, R. et al., 2019).

ZINC
Genes	rs	Minor Allel	Minor Allel Description	Reference
SLC30A8	rs13266634	T	Increased relative risk for increased insulin response due to zinc supplementation predisposition.	(Day, K. J. et al., 2017)
IL6	rs1800795	G	High relative risk for zinc requirement.	(Mocchegiani, E. et al., 2008)

The table above includes genes and their polymorphisms that play a role in zinc metabolism. Insulin metabolism in pancreatic β cells requires Zn, and intracellular Zn acts directly on the intracellular pathways of insulin receptors. Polymorphism in the gene encoding the Zn transporter SLC30A8 (rs13266634) has been identified to be associated with an increased risk of developing type 2 diabetes (T2D), and it has been shown that rs13266634 can alleviate the risk of T2D and impaired glucose regulation in CC carriers by increasing plasma Zn concentrations. These observations support the concept that Zn intervention may play a role in T2D and may benefit from individualization of Zn recommendations based on SLC30A8 (Day, K. J. et al., 2017).

Genetic variations of the IL-6−174G/C locus are involved in IL-6 production and immune response. In particular, older individuals carrying GG genotypes are disadvantaged in terms of longevity and are more prone to develop atherosclerosis due to higher IL-6 production, impaired NK cell cytotoxicity, increased Metallothioneins gene expression, and reduced zinc ion availability. High IL-6 in the elderly causes abnormal increases in MT gene expression, resulting in low zinc ion availability (Mocchegiani, E. et al., 2008).

REFERENCES

Belgemen, T., & Nejat, A. K. A. R. (2004). ÇİNKONUN YAŞAMSAL FONKSİYONLARI VE ÇİNKO METABOLİZMASI İLE İLİŞKİLİ GENLER. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 57(3).

Day, K. J., Adamski, M. M., Dordevic, A. L., & Murgia, C. (2017). Genetic Variations as Modifying Factors to Dietary Zinc Requirements—A Systematic Review. Nutrients, 9(2). https://doi.org/10.3390/nu9020148

Gizlici, M. N., & Çatak, J. (2019). Diabetes mellitus ve çinko ilişkisi. Türkiye Diyabet ve Obezite Dergisi, 3(2), 107-113.

Khankhanian, P., Baranzini, S. E., Johnson, B. A., Madireddy, L., Nickles, D., Croen, L. A., & Wu, Y. W. (2013). Sequencing of the IL6 gene in a case–control study of cerebral palsy in children. BMC Medical Genetics, 14, 126. https://doi.org/10.1186/1471-2350-14-126

Mocchegiani E, Giacconi R, Costarelli L, Muti E, Cipriano C, Tesei S, Pierpaoli S, Giuli C, Papa R, Marcellini F, Gasparini N, Pierandrei R, Piacenza F, Mariani E, Monti D, Dedoussis G, Kanoni S, Herbein G, Fulop T, Rink L, Jajte J, Malavolta M. Zinc deficiency and IL-6 -174G/C polymorphism in old people from different European countries: effect of zinc supplementation. ZINCAGE study. Exp Gerontol. 2008 May;43(5):433-44. doi: 10.1016/j.exger.2008.01.001. Epub 2008 Jan 15. PMID: 18267353.

Rutter GA, Chimienti F. SLC30A8 mutations in type 2 diabetes. Diabetologia. 2015 Jan;58(1):31-6. doi: 10.1007/s00125-014-3405-7. Epub 2014 Oct 7. PMID: 25287711.

Thirunavukkarasu, R., Asirvatham, A. J., Chitra, A., & Jayalakshmi, M. (2019). SLC30A8 Gene rs13266634 C/T Polymorphism in Children with Type 1 Diabetes in Tamil Nadu, India. Journal of Clinical Research in Pediatric Endocrinology, 11(1), 55-60. https://doi.org/10.4274/jcrpe.galenos.2018.2018.0195

ZINC (ZN)