FOKI VITAMIN D RECEPTOR POLYMORPHISM AS A PREDICTOR OF RESPONSE TO HEPATITIS C ANTIVIRAL TREATMENT

  • Noora Hassan Hezam Al-Aqmer Shaikh Zayed Postgraduate Medical Institute, Lahore
  • Soumble Zulfiqar School of Biological Sciences, University of the Punjab, Lahore, Pakistan
  • Sibgha Zulfiqar Department of Physiology, Shaikh Zayed Postgraduate Medical Institute, Shaikh Zayed Medical Complex, Lahore, Pakistan
  • Abdul Rauf Shakoori School of Biological Sciences, University of the Punjab, Lahore, Pakistan
  • Mateen Izhar Department of Microbiology, Shaikh Zayed Hospital, Lahore, Pakistan
Keywords: VDR polymorphism, FokI VDR polymophism, VDR, Polymorphism, Hepatitic C, Vitamin D receptor, Cirrhosis, Anti-viral

Abstract

Background: FokI vitamin D receptor (VDR) genotype ff has been debated as predictor of response to treatment. This study was designed to find out the association of FokI VDR polymorphism with response to chronic hepatitis C daclatasvir- and sofosbuvir-based treatment. Methods: This case control study was conducted at Federal Postgraduate Medical Institute, Lahore from Jan 2019 to Apr 2021. It included 66 chronic hepatitis C genotype 3 patients who responded to daclatasvir and sofosbuvir-based treatment (with ribavirin for cirrhotic patients) and attained sustained virologic response (SVR) three months after complete treatment, and another 66 gender and age matched chronic hepatitis C genotype 3 patients who did not respond to the treatment. Demographic data was collected and 3 mL of blood was drawn from each participant. DNA extraction was done followed by PCR-restriction fragment length polymorphism. Samples were run on 12% polyacrylamide gel and visualized under UV light. Data was analysed using SPSS-24. Results: Frequencies of FokI VDR genotypes FF, Ff, and ff were 54.5%, 28.8%, and 16.7% in responders, and 60.6%, 36.4%, 3.0% in non-responders. There was a significant association between FokI VDR polymorphism and response to treatment (p=0.03). No significant association was found between FokI polymorphism and cirrhosis. Logistic regression showed FokI genotype ff to be a significant predictive factor for a SVR (p=0.041). Conclusion: FokI VDR polymorphism is associated with response to daclatasvir- and sofosbuvir-based antiviral treatment in chronic hepatitis C genotype 3 patients. FokI genotype ff could be considered as a predictive marker for response to treatment.

References

Hepatitis C key facts. WHO. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c (Accessed on 08/22/2021)

World Health Organization. Global hepatitis report 2017. World Health Organization; 2017.

Qureshi H, Bile KM, Jooma R, Alam SE, Afridi HU. Prevalence of hepatitis B and C viral infections in Pakistan: findings of a national survey appealing for effective prevention and control measures. East Mediterr Health J 2010;16 Suppl:S15-23.

Mahmud S, Al Kanaani Z, Abu-Raddad LJ. Characterization of the hepatitis C virus epidemic in Pakistan. BMC Infect Dis 2019;19(1):809.

Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys 2012;523(1):123-33.

Keane JT, Elangovan H, Stokes RA, Gunton JE. Vitamin D and the Liver-Correlation or Cause? Nutrients 2018;10(4):496.

Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 2007;7(9):684-700.

Wu M, Yue M, Huang P, Zhang Y, Xie C, Yu R, et al. Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population. Infect Genet Evol 2016;41:146-52.

Hung CH, Hu TH, Lu SN, Chen CH, Wang JH, Lee CM. Association of vitamin D receptor gene polymorphisms with response to peginterferon plus ribavirin in Asian patients with chronic hepatitis C. J Formos Med Assoc 2016;115(4):278-83.

Shaker O, Nassar Y, Ayoub S, Elrazki M, Zahra A. Impact of FokI (rs10735810) and BsmI (rs1544410) on Treatment of Chronic HCV Patients With Genotype 4. J Clin Lab Anal 2016;30(6):1021-7.

El-Derany MO, Hamdy NM, Al-Ansari NL, El-Mesallamy HO. Integrative role of vitamin D related and Interleukin-28B genes polymorphism in predicting treatment outcomes of Chronic Hepatitis C. BMC Gastroenterol 2016;16:19.

Wang C, Wu Q, Wei XT, Li ZZ, Lei XZ. Association of Vitamin D Receptor Polymorphisms with Response to Antiviral Therapy in Patients with Chronic Hepatitis C. Sichuan Da Xue Xue Bao Yi Xue Ban 2016;47(2):227-31.

García-Martín E, Agúndez JA, Maestro ML, Suárez A, Vidaurreta M, Martínez C, et al. Influence of vitamin D-related gene polymorphisms (CYP27B and VDR) on the response to interferon/ribavirin therapy in chronic hepatitis C. PLoS One 2013;8(9):e74764.

Shehab H, Sabry D, Mukhtar M, Elakel W, Mabrouk M, Zahra A, et al. Vitamin D Receptor FokI Gene Polymorphism Predicted Poor Response to Treatment in Chronic HCV Genotype 4. IJBM 2016;6(4):265-70

Mukhtar M, Sheikh N, Suqaina SK, Batool A, Fatima N, Mehmood R, et al. Vitamin D Receptor Gene Polymorphism: An Important Predictor of Arthritis Development. Biomed Res Int 2019;2019:8326246.

Arai T, Atsukawa M, Tsubota A, Kondo C, Shimada N, Abe H, et al. Vitamin D-related gene polymorphisms do not influence the outcome and serum vitamin D level in pegylated interferon/ribavirin therapy combined with protease inhibitor for patients with genotype 1b chronic hepatitis C. J Med Virol 2015;87(11):1904-12.

Cusato J, Allegra S, Boglione L, De Nicolò A, Baietto L, Cariti G, et al. Vitamin D pathway gene variants and HCV-2/3 therapy outcomes. Antivir Ther 2015;20(3):335-41.

Abdelsalam A, Rashed L, Salman T, Hammad L, Sabry D. Molecular assessment of vitamin D receptor polymorphism as a valid predictor to the response of interferon/ribavirin-based therapy in Egyptian patients with chronic hepatitis C. J Dig Dis 2016;17(8):547-553.

Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004;338(2):143-56.

van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB, et al. The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol 2007;37(2):395-405.

Downloads

Download data is not yet available.
Published
2021-09-30
How to Cite
1.
Al-Aqmer N, Zulfiqar S, Zulfiqar S, Shakoori AR, Izhar M. FOKI VITAMIN D RECEPTOR POLYMORPHISM AS A PREDICTOR OF RESPONSE TO HEPATITIS C ANTIVIRAL TREATMENT. PJP [Internet]. 30Sep.2021 [cited 18Jan.2022];17(3):3-. Available from: https://pjp.pps.org.pk/index.php/PJP/article/view/1384