Evaluation of Vitamin D Receptor Taq I (rs731236) and Bsm I (rs1544410) Gene Polymorphisms in Patients with Chronic Kidney Disease-mineral and Bone Disorder

Hoda A. Abdelsattar; Iris G. Nessim; Mona Mostafa Osman; Abeer Ibrahim Abd Elmageed; Emam A. Waked; Farida M. Khanany

doi:10.3889/oamjms.2023.10631

Authors

Hoda A. Abdelsattar Department of Clinical Pathology, Faculty of Medicine, Ain shams University, Cairo, Egypt https://orcid.org/0000-0002-5883-8207
Iris G. Nessim Department of Clinical Chemistry, Theodor-Bilharz Research Institute, Giza, Egypt https://orcid.org/0000-0003-4408-5790
Mona Mostafa Osman Department of Clinical Pathology, Faculty of Medicine, Ain shams University, Cairo, Egypt https://orcid.org/0000-0003-3907-2565
Abeer Ibrahim Abd Elmageed Department of Clinical Pathology, Faculty of Medicine, Ain shams University, Cairo, Egypt
Emam A. Waked Department of Nephrology, Theodor Bilharz Research Institute, Giza, Egypt https://orcid.org/0000-0003-2422-7456
Farida M. Khanany Department of Clinical Chemistry, Theodor-Bilharz Research Institute, Giza, Egypt https://orcid.org/0000-0001-9380-8612

DOI:

https://doi.org/10.3889/oamjms.2023.10631

Keywords:

TaqI, BsmI, Chronic kidney disease-mineral and bone disorder, Vitamin D receptor gene polymorphism

Abstract

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of the main culprits of increasing morbidity and mortality in patients with stage: 3–5 CKD. Association between Vitamin D receptor (VDR) genetic polymorphisms and CKD-MBD has been inconsistent.

AIM: The aim of the study was to assess the association of VDR Taq I (rs731236) and Bsm I (rs1544410) gene polymorphisms with CKD; and with the development and progression of CKD-MBD.

METHODS: Sixty adult (43–56 years.) Egyptian CKD-MBD male patients (CKD stages: 3–5 with estimated glomerular filtration rate <60 mL/min 1.73 m²) and 30 matched-pair healthy controls were recruited from Theodor-Bilharz Research Institute. Bsm I and Taq I polymorphisms of VDR gene were assessed using restriction fragment length polymorphism-polymerase chain reaction.

RESULTS: CKD-MBD patients having Taq I “tt” mutant gene had a significant decrease in serum 25 hydroxy Vitamin D and a significant elevation of plasma intact parathyroid hormone levels. Having the homotypic “tt” gene variant of VDR Taq I increased the susceptibility to CKD-MBD (Odds ratio [OR]: 19.6, CI: 4.3–89.9 p < 0.01) compared to having the wild “TT” or heterotype “Tt” genotype. Moreover, presence of VDR Taq I “tt” genotype increases OR of having 25 hydroxy Vitamin D deficiency in CKD-MBD patients 7.25 times (CI = 2.21–23.80; p < 0.01).

CONCLUSION: VDR Taq I (rs731236) “tt” genotype increases the susceptibility to CKD-MBD development and progression in Egyptian CKD patients. Moreover, the presence of Taq I “tt” genotype in CKD-MBD patients is independently associated with the risk of developing Vitamin D deficiency.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Cockwell P, Fisher LA. The global burden of chronic kidney disease. Lancet. 2020;395(10225):662-4. https://doi.org/10.1016/S0140-6736(19)32977-0 PMid:32061314 DOI: https://doi.org/10.1016/S0140-6736(19)32977-0

Cannata-Andía JB, Martín-Carro B, Martín-Vírgala J, Rodríguez- Carrio J, Bande-Fernández JJ, Alonso-Montes C, et al. Chronic kidney disease-mineral and bone disorders: Pathogenesis and management. Calcif Tissue Int. 2021;108(4):410-22. https://doi.org/10.1007/s00223-020-00777-1 PMid:33190187 DOI: https://doi.org/10.1007/s00223-020-00777-1

Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl (2011). 2017;7:S1-59. https://doi.org/10.1016/j.kisu.2017.04.001 PMid:30675420 DOI: https://doi.org/10.1016/j.kisu.2017.04.001

Bover J, Ureña-Torres P, Mateu S, DaSilva I, Gràcia S, Sánchez-Baya M, et al. Evidence in chronic kidney disease-mineral and bone disorder guidelines: Is it time to treat or time to wait? Clin Kidney J. 2020;13(4):513-21. https://doi.org/10.1093/ckj/sfz187 PMid:32905295 DOI: https://doi.org/10.1093/ckj/sfz187

Waziri B, Duarte R, Naicker S. Chronic kidney disease-mineral and bone disorder (CKD-MBD): Current perspectives. Int J Nephrol Renovasc Dis. 2019;24:63-276. https://doi:10.2147/IJNRD.S191156 PMid:31920363 DOI: https://doi.org/10.2147/IJNRD.S191156

Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365-408. https://doi.org/10.1152/physrev.00014 PMid:26681795 DOI: https://doi.org/10.1152/physrev.00014.2015

Yang S, Li A, Wang J, Liu J, Han Y, Zhang W, et al. Vitamin D Receptor: A novel therapeutic target for kidney diseases. Curr Med Chem. 2018;25(27):3256-71. https://doi.org/10.2174/0929867325666180214122352 PMid: 29446731 DOI: https://doi.org/10.2174/0929867325666180214122352

Penna-Martinez M, Badenhoop K. Inherited variation in Vitamin D genes and Type I Diabetes predisposition. Genes (Basel). 2017;8(4):125. https://doi.org/10.3390/genes8040125 PMid:28425954 DOI: https://doi.org/10.3390/genes8040125

Mo M, Pan L, Tan L, Jiang L, Pan Y, Li F, et al. Association between VDR gene FokIpolymorphism and renal function in patients with IgA nephropathy. Peer J. 2019;7:e7092. https://doi.org/10.7717/peerj/7092 PMid:31218132 DOI: https://doi.org/10.7717/peerj.7092

Waziri B, Dix-Peek T, Dickens C, Duarte R, Naicker S. Influence of Vitamin D receptor polymorphisms on biochemical markers of mineral bone disorders in South African patients with chronic kidney disease. BMC Nephrol. 2018;19:30. https://doi.org/10.1186/s12882-018-0831-7 DOI: https://doi.org/10.1186/s12882-018-0831-7

Bouksila M, Kaabachi W, Mrad M, Smaoui W, El Kateb EC, Zouaghi MK, et al. FGF 23, PTH and Vitamin D status in end stage renal disease patients affected by VDR Fok I and Bsm I variants. Clin Biochem. 2018;54:42-50. https://doi.org/10.1016/j.clinbiochem.2018.02.009 DOI: https://doi.org/10.1016/j.clinbiochem.2018.02.009

PMid:29458003

Valls J, Cambray S, Pérez-Guallar C, Bozic M, Bermúdez-López M, Fernández E, et al. Association of candidate gene polymorphisms with chronic kidney disease: Results of a case-control analysis in the nefrona cohort. Front Genet. 2019;10:118. https://doi.org/10.3389/fgene.2019.00118 PMid:30863424 DOI: https://doi.org/10.3389/fgene.2019.00118

Divanoglou N, Komninou D, Stea EA, Argiriou A, Papatzikas G, Tsakalof A, et al. Association of Vitamin D receptor gene polymorphisms with serum Vitamin D levels in a Greek rural population (Velestino study). Lifestyle Genom. 2021;14(3):81-90. https://doi.org/10.1159/000514338 PMid:34139712 DOI: https://doi.org/10.1159/000514338

Pourfarzam M, Nia KM, Atapour A, Sadeghi HM. The influence of BsmI and TaqI Vitamin D receptor gene polymorphisms on the intensity of hyperparathyroidism in Iranian hemodialysis patients. Adv Biomed Res. 2014;3:213. https://doi.org/10.4103/2277-9175.143260 PMid:19584489 DOI: https://doi.org/10.4103/2277-9175.143260

Stevens LA, Schmid CH, Zhang YL, Coresh J, Manzi J, Landis R, et al. Development and validation of GFR-estimating equations using diabetes, transplant, and weight. Nephrol Dial Transplant. 2010;25(2):449-57. https://doi.org/10.1093/ndt/gfp510 PMid:19793928 DOI: https://doi.org/10.1093/ndt/gfp510

Nugroho P, Lydia A, Suhardjono S, Harimurti K. Association of BsmI Polymorphisms in the Vitamin D receptor gene among Indonesian population with diabetic kidney disease. Acta Med Indones. 2021;53(2):149-55. PMid:34251342

Yin F, Liu J, Fan M, Zhou X, Zhang X. Association between the Vitamin D receptor gene polymorphisms and diabetic nephropathy risk: A meta-analysis. Nephrology (Carlton). 2018;23:107-16. https://doi.org/10.1111/nep.13111 PMid:28703918 DOI: https://doi.org/10.1111/nep.13111

Yoshihara A, Kaneko N, Iwasaki M, Nohno K, Miyazaki H. Relationship between Vitamin D receptor gene polymorphism and susceptibility to chronic kidney disease and periodontal disease in community-dwelling elderly. J Clin Periodontol. 2018;45(6):672-9. https://doi.org/10.1111/jcpe.12896 PMid:29608804 DOI: https://doi.org/10.1111/jcpe.12896

Manucha W, Juncos LI. The protective role of Vitamin D on the heart and the kidney. Ther Adv Cardiovasc Dis. 2017;11(1):12-9. https://doi.org/10.1177/1753944716675820 PMid:27784812 DOI: https://doi.org/10.1177/1753944716675820

Hussain T, Naushad SM, Ahmed A, Alamery S, Mohammed AA, Abdelkader MO, et al. Association of Vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: A meta-analysis. BMC Med Genet. 2019;20(1):193. https://doi.org/10.1186/s12881-019-0932-6 PMid:31822280 DOI: https://doi.org/10.1186/s12881-019-0932-6

Zhou TB, Jiang ZP, Huang MF. Association of Vitamin D receptor Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the risk of chronic kidney disease. J Receptor Signal Transduct Res. 2014;35(1):58-62. https://doi.org/10.3109/10799893.2014.926928 PMid:24898467 DOI: https://doi.org/10.3109/10799893.2014.926928

Gago EV, Cadarso-Suarez C, Perez-Fernandez R, Burgos RR, Mugica JD, Iglesias CS. Association between Vitamin D FokI polymorphism and serum parathyroid hormone level in patients with chronic renal failure. J Endocrinol Invest. 2005;28(2):117-21. https://doi.org/10.1007/bf03345353 PMid:15887856 DOI: https://doi.org/10.1007/BF03345353

Li L, Wan Q, Yang S, Zhao Q. Impact of Vitamin D receptor gene polymorphism on chronic renal failure susceptibility. Ther Apher Dial. 2018;22(6):575-87. https://doi.org/10.1111/1744-9987.12714 PMid:30058766 DOI: https://doi.org/10.1111/1744-9987.12714