ASSOCIATION OF FOKI RESTRICTION FRAGMENT LENGTH POLYMORPHISM GENOTYPES WITH AUTOIMMUNE THYROID DISEASES
Keywords:
ASSOCIATION OF FOKI RESTRICTION, AUTOIMMUNE THYROID DISEASES
Abstract
Vitamin D, besides its function in regulating the metabolism of calcium-phosphorus, turned out to play an
important immunomodulating role. VDR gene polymorphisms have been investigated for a presumed
association with autoimmune thyroid diseases with conflicting results. The current study was conducted in
Duhok Central Public Health laboratory and the Scientific Research Center/College of Science/University of
Duhok. It included thirty-five autoimmune thyroid patients and thirty-two healthy control subjects. Thyroid
hormones and antithyroid antibody serum levels were assayed. PCR-Restriction fragment length
polymorphism analysis was performed for genotyping and detecting mutations in VDR gene of both patients
and control. The results indicated that no statistically significant difference was found when mean serum
concentrations of thyroid hormones and TSH of patients and controls were compared. While, significant
difference (p<0.05) emerged when the mean serum concentrations of anti-TPO antibodies were compared.
Furthermore, RFLP genotyping analysis by utilizing Fok I restriction enzyme showed that 54.3 % of the
patients belonged to FF genotype, 31.4 % stood for Ff heterozygote genotype, and the last genotype (ff)
involved 14.3 % of the patients. In the control group, 27 (84.4 %) represented FF genotype, the remaining 5
subjects stood for Ff genotype correspondent to 15.6 % of the controls while ff genotype had not been
detected (0 %). In conclusion, different RFLP genotypes of the VDR receptor revealed various levels of
association with AITDs.
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References
Al-Temmemy, R. A. H. (2008). Genetic Biodiversity of some mutations associated with G6PD deficiency among Iraqi patients. Ph D thesis. University of Baghdad. Pp. 72-77.
Altieri, B.; Muscogiuri, G.; Barrea, L.; Mathieu, C.; Vallone, C. V. et al. (2017). Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Rev. Endocr. Metab. Disord.
Annweiler, C.; Llewellyn, D. J.; and Beauchet, O. (2013). Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. J. Alzheim. Dis. 33:659-74.
Arai, H.; Miyamoto, K.; Taketani, Y. et al. (1997). A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J. Bone Miner. Res. 12:915-21.
Baker, A. R.; McDonnell, D. P.; Hughes, M. et al. (1988). Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc. Natl. Acad. Sci. U SA. 85:3294-8.
Bizzaro1, G.; Antico, A.; Fortunato, A.; and Bizzaro, N. (2017). vitamin D and Autoimmune Diseases: is vitamin D Receptor (VDR) polymorphism the Culprit? IMAJ.19: 438–443.
Buttigliero, C.; Monagheddu, C.; and Petroni, P. (2011). Prognostic role of vitamin D status and efficacy of vitamin D supplementation in cancer patients: A systematic review. Oncologist 16:1215-1227.
Chen, S.; Sims, G. P.; Chen, X. X.; Gu, Y.Y.; Chen, S. and Lipsky, P. E. (2007). Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J. Immunol. 179: 1634-47.
Djurovic, J.; Stojkovic, O.; Ozdemir, O.; Silan, F.; Akurut, C.; Todorovic, J.; Savic, K.; and Stamenkovic, G. (2015). Association between FokI, ApaI and TaqI RFLP polymorphisms in VDR gene and Hashimoto’s thyroiditis: preliminary data from female patients in Serbia. Int. J. Immunogenet. 42:190-194.
Dutta, D.; Choudhuri, S.; Mondal, S. A.; Mukherjee, S.; and Chowdhury, S. (2014). Urine albumin creatinine ratio predicts prediabetes progression to diabetes and reversal to normoglycemia: Role of associated insulin resistance, inflammatory cytokines and low Vitamin D. J. Diabetes. 6:316-22.
Eccleshall, T. R.; Garnero, P.; Gross, C.; Delmas, P. D.; and Feldman, DEccleshall, T. R.; Garnero, P.; Gross, C. et al. (1998). Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women: the OFELY Study. J. Bone Miner. Res. 13:31-5.
Effraimidis, G.; Badenhoop, K.; Tijssen, J. G.; and Wiersinga, W. M. (2012). Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc.167(1):43– 8.
Feng, M.; Li, H.; Chen, S. F.; Li, W. F.; and Zhang, F. B. (201323). Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 43(2):318–26.
Goswami, R.; Marwaha, R. K.; Gupta, N.; Tandon, N.; Sreenivas, V.; Tomar, N. et al. (2009). Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey. Br. J. Nutr. 102(3):382–6.
Gross, C.; Eccleshall, T. R.; Malloy, P. J. et al. (1996). The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American women. J. Bone Miner. Res. 11:1850-5.
Guleryuz, B.; Akin, F.; Ata, M. T.; Dalyanoğlu, M. M.; and Turgut, S. (2016). Vitamin-D Receptor (VDR) Gene Polymorphisms (TaqI, FokI) in Turkish Patients with Hashimoto’s Thyroiditis: Relationship to the Levels of Vit-D and Cytokines. Endocrine, Metabolic and Immune Disorders - Drug Targets. 16: 131-139.
Heine, G.; Niesner, U.; Chang H. D.; et al., (2008). “1,25-dihydroxy vitamin D3 promotes IL-10 production in human Bcells,” European Journal of Immunology. 38 (8): 2210–2218.
Huang, Y.; Li, X.; and Wang, M. (2013). Lipoprotein lipase links vitamin D, insulin resistance, and type 2 diabetes: a cross-sectional epidemiological study. Cardiovasc. Diabetol. 12:17.
Huang, Z.L. (2013). The Study on Relationship between Serum 25-Hydroxyvitamin D3 Concentration and Hashimoto Thyroiditis. Master Dissertation, Jilin University, Jilin, China.
Imtiaz, S.; Siddiqui, N.; Raza, A.; loya, A.; and Muhammad, A. (2012). Vitamin D deficiency in newly diagnosed breast cancer patients. Indian J. Endocrinol. Metab. 6: 409-413.
Inoue, N.; Watanabe, M.; Ishido, N.; Katsumata, Y.; Kagawa, T.; Hidaka, Y. et al. (2014). The functional polymorphisms of VDR, GC, and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin. Exp. Immunol. 178(2):262–9.
Institute of Medicine. (2011). Dietary reference intakes for calcium and vitamin D. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB (Eds), National Academic Press, Washington, DC, USA.
Khammissa, R.A.G.; Fourie, J.; Motswaledi, M.H.; Ballyram, R.; Lemmer, J.; and Feller, L. (2018). “The biological activities of vitamin D and Its receptor in relation to calcium and bone homeostasis, cancer, immune and cardio vascular systems, skin biology, and oral health,”Bio Med ResearchI nternational. (2018), article ID 9276380, 9 pages.
Kim, D. (2017). The Role of Vitamin D in Thyroid Diseases. A review. Int. J. Mol. Sci. 18 (1949):1-19.
Kostner, K.; Denzer, N.; Muller, C.S.L.; et al. (2009). The Relevance of Vitamin D Receptor (VDR) Gene Polymorphisms for Cancer: A Review of the Literature. Anticancer Research. 29: 3511-3536.
Lin, W.Y.; Wan, L.; Tsai, C.H.; Chen, R.H.; Lee, C.C.; and Tsai, F.C. (2006). Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto’s thyroiditis in Chinese patients in Taiwan. J. Clin. Lab. Anal. 20: 109- 112.
Meng, S.; He, S. T.; Jiang, W. J.; Xiao, L.; Li, D. F.; Xu, J. et al. (2015). Genetic susceptibility to autoimmune thyroid diseases in a Chinese Han population: Role of vitamin D receptor gene polymorphisms. Ann. Endocrinol. (Paris). 76(6):684-9.
Morrison, N. A.; Yeoman, R.; Kelly, P. J. et al. (1992). Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc. Natl. Acad. Sci. USA: 89:6665-9.
Sakharkar, P.; Deb, S.; and Vu, Don. (2017). Vitamin D Receptor (VDR) Gene Polymorphism: Implications on Non-Bone Diseases. Journal of Basic and Clinical Pharmacy. 8: S2: S006-S0010.
Sambrook, J.; Fritsch, E. F.; and Maniatis, T. (1989). Molecular cloning: A laboratory manual. 2nd ed, Cold spring harbor laboratory press, cold spring Harbor, New York.
Wang, J.; Lv, S.; Chen, G.; Gao, C.; He, J.; Zhong, H.; et. al. (2015). Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 7(4):2485–98.
Yazici, D.; Yavuz, D.; Tarcin, O.; Sancak, S.; Deyneli, O.; and Akalin, S. (2013). Vitamin D receptor gene ApaI, TaqI, FokI and BsmI polymorphisms in a group of Turkish patients with Hashimoto’s thyroiditis. Minerva. Endocrinol. 38: 195-201.
Zarrin, R.; Bagheri, M.; Mehdizadeh, A.; Ayremlou, P.; and Faghfouri, A. H. (2018). The association of FokI and ApaI polymorphisms in vitamin D receptor gene with autoimmune thyroid diseases in the northwest of Iran. Med. J. Islam Repub. Iran. 32:4.
Altieri, B.; Muscogiuri, G.; Barrea, L.; Mathieu, C.; Vallone, C. V. et al. (2017). Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Rev. Endocr. Metab. Disord.
Annweiler, C.; Llewellyn, D. J.; and Beauchet, O. (2013). Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. J. Alzheim. Dis. 33:659-74.
Arai, H.; Miyamoto, K.; Taketani, Y. et al. (1997). A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J. Bone Miner. Res. 12:915-21.
Baker, A. R.; McDonnell, D. P.; Hughes, M. et al. (1988). Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc. Natl. Acad. Sci. U SA. 85:3294-8.
Bizzaro1, G.; Antico, A.; Fortunato, A.; and Bizzaro, N. (2017). vitamin D and Autoimmune Diseases: is vitamin D Receptor (VDR) polymorphism the Culprit? IMAJ.19: 438–443.
Buttigliero, C.; Monagheddu, C.; and Petroni, P. (2011). Prognostic role of vitamin D status and efficacy of vitamin D supplementation in cancer patients: A systematic review. Oncologist 16:1215-1227.
Chen, S.; Sims, G. P.; Chen, X. X.; Gu, Y.Y.; Chen, S. and Lipsky, P. E. (2007). Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J. Immunol. 179: 1634-47.
Djurovic, J.; Stojkovic, O.; Ozdemir, O.; Silan, F.; Akurut, C.; Todorovic, J.; Savic, K.; and Stamenkovic, G. (2015). Association between FokI, ApaI and TaqI RFLP polymorphisms in VDR gene and Hashimoto’s thyroiditis: preliminary data from female patients in Serbia. Int. J. Immunogenet. 42:190-194.
Dutta, D.; Choudhuri, S.; Mondal, S. A.; Mukherjee, S.; and Chowdhury, S. (2014). Urine albumin creatinine ratio predicts prediabetes progression to diabetes and reversal to normoglycemia: Role of associated insulin resistance, inflammatory cytokines and low Vitamin D. J. Diabetes. 6:316-22.
Eccleshall, T. R.; Garnero, P.; Gross, C.; Delmas, P. D.; and Feldman, DEccleshall, T. R.; Garnero, P.; Gross, C. et al. (1998). Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women: the OFELY Study. J. Bone Miner. Res. 13:31-5.
Effraimidis, G.; Badenhoop, K.; Tijssen, J. G.; and Wiersinga, W. M. (2012). Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc.167(1):43– 8.
Feng, M.; Li, H.; Chen, S. F.; Li, W. F.; and Zhang, F. B. (201323). Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 43(2):318–26.
Goswami, R.; Marwaha, R. K.; Gupta, N.; Tandon, N.; Sreenivas, V.; Tomar, N. et al. (2009). Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey. Br. J. Nutr. 102(3):382–6.
Gross, C.; Eccleshall, T. R.; Malloy, P. J. et al. (1996). The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American women. J. Bone Miner. Res. 11:1850-5.
Guleryuz, B.; Akin, F.; Ata, M. T.; Dalyanoğlu, M. M.; and Turgut, S. (2016). Vitamin-D Receptor (VDR) Gene Polymorphisms (TaqI, FokI) in Turkish Patients with Hashimoto’s Thyroiditis: Relationship to the Levels of Vit-D and Cytokines. Endocrine, Metabolic and Immune Disorders - Drug Targets. 16: 131-139.
Heine, G.; Niesner, U.; Chang H. D.; et al., (2008). “1,25-dihydroxy vitamin D3 promotes IL-10 production in human Bcells,” European Journal of Immunology. 38 (8): 2210–2218.
Huang, Y.; Li, X.; and Wang, M. (2013). Lipoprotein lipase links vitamin D, insulin resistance, and type 2 diabetes: a cross-sectional epidemiological study. Cardiovasc. Diabetol. 12:17.
Huang, Z.L. (2013). The Study on Relationship between Serum 25-Hydroxyvitamin D3 Concentration and Hashimoto Thyroiditis. Master Dissertation, Jilin University, Jilin, China.
Imtiaz, S.; Siddiqui, N.; Raza, A.; loya, A.; and Muhammad, A. (2012). Vitamin D deficiency in newly diagnosed breast cancer patients. Indian J. Endocrinol. Metab. 6: 409-413.
Inoue, N.; Watanabe, M.; Ishido, N.; Katsumata, Y.; Kagawa, T.; Hidaka, Y. et al. (2014). The functional polymorphisms of VDR, GC, and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin. Exp. Immunol. 178(2):262–9.
Institute of Medicine. (2011). Dietary reference intakes for calcium and vitamin D. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB (Eds), National Academic Press, Washington, DC, USA.
Khammissa, R.A.G.; Fourie, J.; Motswaledi, M.H.; Ballyram, R.; Lemmer, J.; and Feller, L. (2018). “The biological activities of vitamin D and Its receptor in relation to calcium and bone homeostasis, cancer, immune and cardio vascular systems, skin biology, and oral health,”Bio Med ResearchI nternational. (2018), article ID 9276380, 9 pages.
Kim, D. (2017). The Role of Vitamin D in Thyroid Diseases. A review. Int. J. Mol. Sci. 18 (1949):1-19.
Kostner, K.; Denzer, N.; Muller, C.S.L.; et al. (2009). The Relevance of Vitamin D Receptor (VDR) Gene Polymorphisms for Cancer: A Review of the Literature. Anticancer Research. 29: 3511-3536.
Lin, W.Y.; Wan, L.; Tsai, C.H.; Chen, R.H.; Lee, C.C.; and Tsai, F.C. (2006). Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto’s thyroiditis in Chinese patients in Taiwan. J. Clin. Lab. Anal. 20: 109- 112.
Meng, S.; He, S. T.; Jiang, W. J.; Xiao, L.; Li, D. F.; Xu, J. et al. (2015). Genetic susceptibility to autoimmune thyroid diseases in a Chinese Han population: Role of vitamin D receptor gene polymorphisms. Ann. Endocrinol. (Paris). 76(6):684-9.
Morrison, N. A.; Yeoman, R.; Kelly, P. J. et al. (1992). Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc. Natl. Acad. Sci. USA: 89:6665-9.
Sakharkar, P.; Deb, S.; and Vu, Don. (2017). Vitamin D Receptor (VDR) Gene Polymorphism: Implications on Non-Bone Diseases. Journal of Basic and Clinical Pharmacy. 8: S2: S006-S0010.
Sambrook, J.; Fritsch, E. F.; and Maniatis, T. (1989). Molecular cloning: A laboratory manual. 2nd ed, Cold spring harbor laboratory press, cold spring Harbor, New York.
Wang, J.; Lv, S.; Chen, G.; Gao, C.; He, J.; Zhong, H.; et. al. (2015). Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 7(4):2485–98.
Yazici, D.; Yavuz, D.; Tarcin, O.; Sancak, S.; Deyneli, O.; and Akalin, S. (2013). Vitamin D receptor gene ApaI, TaqI, FokI and BsmI polymorphisms in a group of Turkish patients with Hashimoto’s thyroiditis. Minerva. Endocrinol. 38: 195-201.
Zarrin, R.; Bagheri, M.; Mehdizadeh, A.; Ayremlou, P.; and Faghfouri, A. H. (2018). The association of FokI and ApaI polymorphisms in vitamin D receptor gene with autoimmune thyroid diseases in the northwest of Iran. Med. J. Islam Repub. Iran. 32:4.
Published
2020-09-12
How to Cite
HANON, R. A. (2020). ASSOCIATION OF FOKI RESTRICTION FRAGMENT LENGTH POLYMORPHISM GENOTYPES WITH AUTOIMMUNE THYROID DISEASES. Journal of Duhok University, 23(1), 126-133. https://doi.org/10.26682/sjuod.2020.23.1.13
Section
Pure and Engineering Sciences
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