Recent Doctor of Medicine Study Reveals Gene Polymorphisms and the Risk of HIV-TB Coinfection

Recent Doctor of Medicine Study Reveals Gene Polymorphisms and the Risk of HIV-TB Coinfection


Located in Dr. A.A.Made Djelantik, Faculty of Medicine Building, Udayana University, Denpasar, the Doctoral Promotion exam took place with Promovenda candidate Dr. Anak Agung Ayu Yuli Gayatri, Sp.PD-KPTI, FINASIM with the dissertation title "FokI Polymorphism of the Gene Encoding Vitamin D Receptor, Microtubule-Associated Proteins 1A/1B- Light Chain 3 and Low Caspase 3 as a Risk Factor for Tuberculosis Coinfection in Human Immunodeficiency Virus Patients " (28/3/2024)


The target of eliminating Human Immunodeficiency Virus-Tuberculosis (HIV-TB) co-infection, which are two major health problems in the world, is still difficult to achieve. Until now, there is no clear method for identifying groups of people living with HIV (PLHIV) who will experience active TB.


The FokI polymorphism of the vitamin D receptor (VDR) gene probably plays a role in complex signaling in the immune system to fight Mycobacterium tuberculosis (Mtb) infection through activation of defensive processes, namely autophagy and apoptosis. This study aims to analyze the role of the FokI polymorphism of the VDR coding gene, as well as low levels of MicrotubuleAssociated Proteins 1a/1b- Light Chain3 (LC3) as a parameter for inhibiting autophagy and low caspase 3 as a parameter for inhibiting apoptosis as a risk factor for HIV-TB co-infection.


This study used a case control design with a sample size of 30 HIV-TB patients as the case group and 30 HIV patients without TB as the control group. The FokI polymorphism of the VDR gene was detected by PCR and sequencing, and LC3 levels and caspase 3 levels were measured by ELISA at the Integrated Biomedical Laboratory Unit, Faculty of Medicine, Udayana University. Data analysis for different proportions used bivariate tests followed by relationship analysis tests using logistic regression.


The results of examination of the Fok1 polymorphism of the VDR rs2228570 gene in research subjects found that the proportion of the f allele (genotypes ff and Ff) in the case group was 26 (86.7%) people and controls 13 (43.3%) people. The results of serum LC3 measurements showed low LC3 (LC3 ≤30 ng/mL) in the case group of 27 (90%) people and 9 (30%) controls. Low caspase 3 levels (caspase 3 ≤ 3 ng/mL) were found in the case group of 28 (93.3%) people and in the controls 15 (50%) people. Of the three main variables studied in the logistic regression analysis, it was found that the FokI polymorphism of the VDR FokI gene f allele and low LC3 was proven to be clinically and statistically significant as a risk factor for HIV-TB co-infection. Meanwhile, low caspase 3 in logistic regression analysis showed clinical significance as a risk factor for HIV-TB co-infection with an adjusted RO value = 7.448 which was higher than the expected RO although the p value = 0.070 was not statistically significant.


From the research results, it can be concluded that the FokI polymorphism of the gene encoding VDR f allele and clinically low levels of serum LC3 and caspase 3 are risk factors for TB in HIV. Thus, the results of this study can be used as a basis for developing further research regarding TB risk parameters in HIV, so that they can be applied to clinical practice in treating HIV-TB co-infection.


This exam was led by the Deputy Dean for Academic Affairs and Planning, FK Unud Dr.dr.I Gede Eka Wiratnaya, Sp.OT (K)., with a team of examiners:

1. Prof. Dr. Dr. Ketut Tuti Parwati Merati, Sp.PD-KPTI., FINASIM (Promoter)

2.Dr. rer. Nat. Dr. Ni Nyoman Ayu Dewi, M.Si (Copromotor II)

3. Prof. Dr. Dr. I Made Bakta, Sp.PD-KHOM

4. Prof. Dr. Dr. I Made Jawi, M. Kes

5. Prof. Dr. Ir. Ida Bagus Putra Manuaba, M.Phil

6. Prof. Dr. Dr. I Wayan Putu Sutirta Yasa, M.Si

7. Prof. Dr. dr. A.A.Wiradewi Lestari,Sp.PK(K)

8. Dr. dr. Urged Made Wihandani, M.Kes

9. Dr. dr. Wira Gotera, Sp.PD-KEMD-FINASIM


Meanwhile, academic invitations are:

1.Dr. Dr. I Ketut Agus Somia, Sp.PD-KPTI, FINASIM

2.Dr. Dr. Yenny Kandarini, Sp.PD., KGH

3.Dr. Dr. I Gusti Putu Suka Aryana, Sp.PD, K-Ger, FINASIM

4.Dr. Dr. I Putu Eka Widyadharma, M.Sc., Sp.S(K)

5.Dr. Dr. Ni Made Adi Tarini, Sp.MK(K)


In this exam, Dr. Dr. Anak Agung Ayu Yuli Gayatri, Sp.PD-KPTI, FINASIM, was declared to have graduated as the 412th Doctoral Graduate of the Medical Science Doctoral Degree Study Program with cum laude predicate.