https://doi.org/10.4081/monaldi.2025.3329
Impact of vitamin D receptor gene polymorphism on susceptibility to tuberculosis infection in Indonesia
Submitted: January 3, 2025
Accepted: February 3, 2025
Published: April 24, 2025
Accepted: February 3, 2025
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
This study investigated the association between vitamin D receptor (VDR) gene polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in various ethnic groups in Indonesia. The study involved 267 participants divided into three groups: 99 healthy controls, 80 individuals with latent tuberculosis, and 88 with active tuberculosis. Four VDR polymorphisms (FokI, ApaI, BsmI, and TaqI) were analyzed using polymerase chain reaction and restriction fragment length polymorphism. The research comprehensively analyzes sociodemographic and genetic factors associated with PTB in Indonesia, focusing on three ethnic groups—Makassar, Bugis, and Toraja. Sociodemographic data (n=267) revealed a mean age of 34.43±11.81 years, with a higher prevalence of males (55.4%) and significant associations between PTB status and education level (p=0.006). Smoking was notably higher among active PTB patients (48.9%), emphasizing behavioral influences on disease prevalence. The genetic study (n=88 PTB, n=179 controls) highlighted significant associations of VDR gene polymorphisms with PTB. Specifically, the FokI CC genotype (p=0.014) and C allele (p<0.001) were more frequent in PTB patients, alongside the ApaI GT genotype (p<0.001) and BsmI GG genotype (p<0.001). The findings emphasize the multifactorial nature of PTB susceptibility, highlighting the roles of genetic variations, particularly in the VDR gene, and sociodemographic factors in influencing PTB risk in Indonesian populations.
Mejbel FAH, Aljanaby IAJ, Aljanaby AAJ. Pulmonary tuberculosis risks and challenges. E3S Web of Conf 2023;381:01101.
DOI: https://doi.org/10.1051/e3sconf/202338101101
Mohajan H. Tuberculosis is a fatal disease among some developing countries of the world. 2014. Available from: https://mpra.ub.uni-muenchen.de/82851/1/MPRA_paper_82851.pdf.
Sulis G, Roggi A, Matteelli A, Raviglione MC. Tuberculosis: epidemiology and control. Mediterr J Hematol Infect Dis 2014;6:e2014070.
DOI: https://doi.org/10.4084/mjhid.2014.070
Crawford LS, Romaniuk SN. Containing a global threat: the virulence of tuberculosis in developed and developing countries. Glob J Health Sci 2011;3:77.
DOI: https://doi.org/10.5539/gjhs.v3n1p77
Gao L, Tao Y, Zhang L, Jin Q. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis. Int J Tuberc lung Dis 2010;14:15-23.
YIM J, Selvaraj P. Genetic susceptibility in tuberculosis. Respirology 2010;15:241-56.
DOI: https://doi.org/10.1111/j.1440-1843.2009.01690.x
Möller M, De Wit E, Hoal EG. Past, present and future directions in human genetic susceptibility to tuberculosis. FEMS Immunol Med Microbiol 2010;58:3-26.
DOI: https://doi.org/10.1111/j.1574-695X.2009.00600.x
Hasan SI. The role of genes and genetic variation in human tuberculosis susceptibility: a population perspective. Uttar Pradesh J Zool. 2024;45:41-51.
DOI: https://doi.org/10.56557/upjoz/2024/v45i53929
Chen C, Liu Q, Zhu L, Yang H, Lu W. Vitamin D receptor gene polymorphisms on the risk of tuberculosis, a meta-analysis of 29 case-control studies. PLoS One 2013;8:e83843.
DOI: https://doi.org/10.1371/journal.pone.0083843
Salimi S, Farajian-Mashhadi F, Alavi-Naini R, et al. Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis. Biomed Rep 2015;3:189-94.
DOI: https://doi.org/10.3892/br.2014.402
Panda S, Tiwari A, Luthra K, et al. Association of Fok1 VDR polymorphism with vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts. Sci Rep 2019;9:15251.
DOI: https://doi.org/10.1038/s41598-019-51803-8
Tao R, Xiao S, Wang L, et al. Association between vitamin D receptor gene polymorphisms and susceptibility to tuberculosis: a systematic review and meta-analysis. Front Genet 2024;15:1382957.
DOI: https://doi.org/10.3389/fgene.2024.1382957
Mohammadi A, Khanbabaei H, Nasiri-Kalmarzi R, et al. Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: a systematic review and meta-analysis. J Microbiol Immunol Infect 2020;53:827-35.
DOI: https://doi.org/10.1016/j.jmii.2019.08.011
de Albuquerque Borborema ME, de Souza Pereira JJ, dos Santos Peixoto A, et al. Differential distribution in vitamin D receptor gene variants and expression profile in northeast Brazil influences upon active pulmonary tuberculosis. Mol Biol Rep 2020;47:7317-22.
DOI: https://doi.org/10.1007/s11033-020-05762-3
Ates O, Dolek B, Dalyan L, et al. The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis. Mol Biol Rep 2011;38:2633-6.
DOI: https://doi.org/10.1007/s11033-010-0404-8
Fernández-Mestre M, Villasmil Á, Takiff H, Alcalá ZF. NRAMP1 and VDR gene polymorphisms in susceptibility to tuberculosis in Venezuelan population. Dis Markers 2015;2015:860628.
DOI: https://doi.org/10.1155/2015/860628
Sekhar Miraj S, Vyas N, Kurian SJ, et al. Vitamin D receptor gene polymorphism and vitamin D supplementation on clinical/treatment outcome in tuberculosis: current and future perspectives. Expert Rev Anti Infect Ther 2022;20:1179-86.
DOI: https://doi.org/10.1080/14787210.2022.2081546
Palmirotta R, Ferroni P, Ludovici G, et al. VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension. Clin Biochem 2010;43:1090-5.
DOI: https://doi.org/10.1016/j.clinbiochem.2010.06.020
Marashian SM, Farnia P, Seyf S, et al. Evaluating the role of vitamin D receptor polymorphisms on susceptibility to tuberculosis among iranian patients: a case-control study. Tuberk Toraks 2010;58:147-58.
Chobanian A V, Bakris GL, Black HR, et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003;42:1206-52.
DOI: https://doi.org/10.1161/01.HYP.0000107251.49515.c2
Hall S, Vincenzi DA. Software: SPSS for Windows SPSS Inc. 233 S. Wacker Dr., 11th Floor Chicago, IL 60606 (312) 651-3000 www.spss.com. Ergon Des Q Hum Factors Appl 2001;9:27-9.
DOI: https://doi.org/10.1177/106480460100900307
Zhang Y, Hedo R, Rivera A, et al. Post hoc power analysis: is it an informative and meaningful analysis? Gen Psychiatr 2019;32:e100069.
DOI: https://doi.org/10.1136/gpsych-2019-100069
Stevens H, Ximenes RAA, Dantas OMS, Rodrigues LC. Risk factors for tuberculosis in older children and adolescents: a matched case–control study in Recife, Brazil. Emerg Themes Epidemiol 2014;11:20.
DOI: https://doi.org/10.1186/s12982-014-0020-5
Wang J, Shen H. Review of cigarette smoking and tuberculosis in China: intervention is needed for smoking cessation among tuberculosis patients. BMC Public Health 2009;9:292.
DOI: https://doi.org/10.1186/1471-2458-9-292
Horne DJ, Campo M, Ortiz JR, et al. Association between smoking and latent tuberculosis in the US population: an analysis of the National Health and Nutrition Examination Survey. PLoS One 2012;7:e49050.
DOI: https://doi.org/10.1371/journal.pone.0049050
Watkins RE, Plant AJ. Does smoking explain sex differences in the global tuberculosis epidemic? Epidemiol Infect 2006;134:333-9.
DOI: https://doi.org/10.1017/S0950268805005042
Rappoport N, Toung J, Hadley D, et al. A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth. Sci Rep 2018;8:226.
DOI: https://doi.org/10.1038/s41598-017-18246-5
Barchitta M, Maugeri A, La Rosa MC, et al. Single nucleotide polymorphisms in vitamin D receptor gene affect birth weight and the risk of preterm birth: results from the “mamma & bambino” cohort and a meta-analysis. Nutrients 2018;10:1172.
DOI: https://doi.org/10.3390/nu10091172
Sheikh IA, Ahmad E, Jamal MS, et al. Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update. BMC Genomics 2016;17:39-50.
DOI: https://doi.org/10.1186/s12864-016-3089-0
O’Callaghan ME, MacLennan AH, McMichael GL, et al. Single-nucleotide polymorphism associations with preterm delivery: a case–control replication study and meta-analysis. Pediatr Res 2013;74:433-8.
DOI: https://doi.org/10.1038/pr.2013.117
Areeshi MY, Mandal RK, Dar SA, et al. A reappraised meta-analysis of the genetic association between Vitamin D receptor Bsm I (rs1544410) polymorphism and pulmonary tuberculosis risk. Biosci Rep 2017;37:BSR20170247.
DOI: https://doi.org/10.1042/BSR20170247
Selvaraj P, Chandra G, Kurian SM, et al. Association of vitamin D receptor gene variants of BsmI, ApaI and FokI polymorphisms with susceptibility or resistance to pulmonary tuberculosis. Curr Sci 2003;1564-8.
Silva-Ramírez B, Saenz-Saenz CA, Bracho-Vela LA, et al. Association between vitamin D receptor gene polymorphisms and pulmonary tuberculosis in a Mexican population. Indian J Tuberc 2019;66:70-5.
DOI: https://doi.org/10.1016/j.ijtb.2018.04.005
Hu Q, Chen Z, Liang G, et al. Vitamin D receptor gene associations with pulmonary tuberculosis in a Tibetan Chinese population. BMC Infect Dis 2016;16:469.
DOI: https://doi.org/10.1186/s12879-016-1699-4
Li B, Wen F, Wang Z. Correlation between polymorphism of vitamin D receptor TaqI and susceptibility to tuberculosis: an update meta-analysis. Medicine 2022;101:e29127.
DOI: https://doi.org/10.1097/MD.0000000000029127
Lee YH, Song GG. Vitamin D receptor gene FokI, TaqI, BsmI, and ApaI polymorphisms and susceptibility to pulmonary tuberculosis: a meta-analysis. Genet Mol Res 2015;14:9118-29.
DOI: https://doi.org/10.4238/2015.August.7.21
Miao R, Huang S, Li C, et al. An HLA class II locus, previously identified by a genome-wide association study, is also associated with susceptibility to pulmonary tuberculosis in a Chinese population. Infect Genet Evol 2018;64:164-7.
DOI: https://doi.org/10.1016/j.meegid.2018.06.022
Lu T, Wang M, Liu N, et al. Transporter associated with antigen processing 1 gene polymorphisms increase the susceptibility to tuberculosis. Pharmgenomics Pers Med 2023;16:325-36.
DOI: https://doi.org/10.2147/PGPM.S404339
Sinaga BYM, Amin M, Siregar Y, Sarumpaet SM. Correlation between Vitamin D receptor gene FOKI and BSMI polymorphisms and the susceptibility to pulmonary tuberculosis in an Indonesian Batak-ethnic population. Acta Med Indones 2014;46:275-82.
Sadykov M, Azizan A, Kozhamkulov U, et al. Association of genetic variations in the vitamin D pathway with susceptibility to tuberculosis in Kazakhstan. Cancer Sci 2017;15:1659-66.
DOI: https://doi.org/10.1007/s11033-020-05255-3
Ethics Approval
This research has received ethical approval from the Health Research Ethics Committee of Makassar Health Polytechnic No. 1070/M/KEPK- PTKMKS/VII/2024 July 2024.How to Cite
Ismail, Ismail, Ratnawati Ratnawati, Yulianto Machmud, and Harliani Harliani. 2025. “Impact of Vitamin D Receptor Gene Polymorphism on Susceptibility to Tuberculosis Infection in Indonesia”. Monaldi Archives for Chest Disease, April. https://doi.org/10.4081/monaldi.2025.3329.
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