HLA-DQ Allele Carriers as Genetic Risk Factors for Pulmonary Tuberculosis: A Meta-Analysis
DOI:
https://doi.org/10.6000/1929-6029.2026.15.04Keywords:
PTB, allele carriers, HLA-DQ, HLA-DQA1, HLA-DQB1, meta-analysisAbstract
Several studies have shown that pulmonary tuberculosis (PTB) is a major global health issue, affecting various countries around the world. Susceptibility to the disease has been reported to be influenced by host genetic variables, including Human Leukocyte Antigen (HLA) class II genes, specifically HLA-DQ. Despite the association, studies on the relationship between HLA-DQ allele carriers and the risk of PTB are still not consistent among various populations. This meta-analysis aims to assess the association between carrier status (phenotype frequency) of HLA-DQA1 and HLA-DQB1 alleles and susceptibility to pulmonary tuberculosis. Several HLA-DQ alleles were examined, and the pooled effect size estimates were calculated based on carrier (phenotype) frequencies of HLA-DQA1 and HLA-DQB1 alleles, using odds ratios (ORs) and 95% confidence intervals (CI). A total of 21 high-quality studies (NOS ≥7) were included in the review, with 25,896 controls and 3,927 cases. The results showed that the risk of PTB was significantly increased by allele carriers of HLA-DQA1*01:01 (OR = 1.79; 95% CI: 1.22–2.62) and HLA-DQA1*03:01 (OR = 1.64; 95% CI: 1.08–2.48). Risk factors for HLA-DQB1 allele carriers were also found to be the *02:01 (OR = 1.36; 95% CI: 1.04–1.79), *05:03 (OR = 1.35; 95% CI: 1.01–1.80), and *06:01 (OR = 1.41; 95% CI: 1.00–1.97) allele carriers. Meanwhile, HLA-DQA1*02:01, *04:01, *05:01, and *06:01 allele carriers had protective effects. The majority of analyses found no indications of publication bias. This meta-analysis demonstrates that carrier status of specific HLA-DQA1 and HLA-DQB1 alleles is significantly associated with susceptibility to pulmonary tuberculosis
References
Salari N, Kanjoori AH, Hosseinian-Far A, Hasheminezhad R, Mansouri K, Mohammadi M. Global prevalence of drug-resistant tuberculosis: a systematic review and meta-analysis. Infect Dis Poverty 2023; 12(1): 1-12.
WHO. Global tuberculosis report 2024. 2024.
Cords O, et al. Incidence and prevalence of tuberculosis in incarcerated populations: a systematic review and meta-analysis. Lancet Public Heal 2021; 6(5): e300-e308.
Wahyuningsih S, et al. An analysis of risk factors for Multidrug Resistant Tuberculosis (MDR-TB): a hospital-based study. J Public Heal Dev 2023; 21(2): 91-101.
Aravindan P. Host genetics and tuberculosis: Theory of genetic polymorphism and tuberculosis. Lung India 2019; 36(3): 244-252.
Naidoo L, Arumugam T, Ramsuran V. Host Genetic Impact on Infectious Diseases among Different Ethnic Groups. Adv Genet 2023; 4(4): 1-22.
Kinnear C, Hoal EG, Schurz H, van Helden PD, Möller M. The role of human host genetics in tuberculosis resistance. Expert Rev Respir Med 2017; 11(9): 721-737.
Marianna Orlova ES. Human Genomics of Mycobacterium Tuberculosis Infection and Disease. HHS Public Access 2017; 5(3): 125-131.
Mozzi A, Pontremoli C, Sironi M. Genetic susceptibility to infectious disease: Crrent stattus and future perspectives from genome-wide approaches. Infect Genet Evol jo 2018; 66: 286-307.
Wamala D, Buteme HK, Kirimunda S, Kallenius G, Joloba M. Association between human leukocyte antigen class II and pulmonary tuberculosis due to mycobacterium tuberculosis in Uganda. BMC Infect Dis 2016; 16(1): 1-6.
Liu Bingnan RF, Yuanyuan S. Current research status of HLA in immune‐related diseases.pdf. Immunity. Inflamm Dis 2021; 9: 340-350.
Zhou X, Zhou Q, Yang ZF, Li WX. Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug-resistant and rifampicin-resistant tuberculosis in Han Chinese from Hubei Province. Int J Immunogenet 2018; 45(1): 8-21.
Zheng R, et al. Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese. Nat Commun 2018; 9(1): 1-9.
Larcombe LA, et al. HLA - A, B, DRB1, DQA1, DQB1 alleles and haplotype frequencies in Dene and Cree cohorts in Manitoba, Canada. Hum Immunol 2017; 78(5-6): 401-411.
Soha A, et al. HLA class II DRB1, DQA1, DQB1 loci in patients with HIV infection and tuberculosis in a Latvian cohort group. Clin Immunol 2024; 49(1): 37-44.
Baniaghil S, Borujeni GN, Tajbakhsh H, Esmailnejad A, Amirzargar AA. HLA-DRB1, DQB1 allele frequencies in Iranian patients (sistani ethnic) with tuberculosis and healthy control. Tehran Univ Med J 2017; 75(3): 72-178.
Chihab LY, et al. Expression of specific HLA class II alleles is associated with an increased risk for active tuberculosis and a distinct gene expression profile. Hla 2023; 101(2): 124-137.
Toyo-oka L, et al. Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis. Hla 2017; 90(3): 149-156.
Siddaway AP, Wood AM, Hedges LV. How to Do a Systematic Review: A Best Practice Guide for Conducting and Reporting Narrative Reviews, Meta-Analyses, and Meta-Syntheses. Annu Rev Psychol 2019; 70: 747-770.
Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: A comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res 2014; 14(579): 1-10.
Wells GA, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. in Ottawa Hospital Research Institute, Oxford, 2021. [Online]. Available: https://www.ohri.ca/programs/ clinical_epidemiology/oxford.asp
Higgins JPT, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. cochrane handbook for systematic reviews of interventions version 6.4 (updated August 2023). cochrane, 2023, 2024.
Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634.
Cochrane. RevMan Trusted evidence. Informed decisions. Better health 2025. https://revman.cochrane.org/ (accessed May 21, 2025).
Page MJ, et al. The PRISMA 2020 statement : an updated guideline for reporting systematic reviews Systematic reviews and Meta-Analyses. BMJ 2021; 372(71).
Tang NL, et al. Genetic susceptibility to Tuberculosis : Interaction between HLA-DQA1 and age of onset. Infect Genet Evol 2019; 68: 98-104.
Li M, et al. A next generation sequencing combined genome-wide association study identifies novel tuberculosis susceptibility loci in Chinese population. Genomics 2021; 113(4): 2377-2384.
Goldfeld AE, et al. Association of an HLA-DQ allele with clinical tuberculosis. JAMA 1998; 279(3): 226-228.
Ravikumar M, et al. Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India. Tuber Lung Dis 1999; 79(5): 309-317.
Terán-Escandón D, et al. Human leukocyte antigen-associated susceptibility to pulmonary tuberculosis: Molecular analysis of class II alleles by DNA amplification and oligonucleotide hybridization in Mexican patients. Chest 1999; 115(2): 428-433.
Vejbaesya S, Chierakul N, Luangtrakool K, Srinak D, Stephens HAF. Associations of HLA class II alleles with pulmonary tuberculosis in thais. Eur J Immunogenet 2002; 29(5): 431-434.
Sharma SK, et al. Clinical and genetic risk factors for the development of multi-drug resistant tuberculosis in non-HIV infected patients at a tertiary care center in India: A case-control study. Infect Genet Evol 2003; 3(3): 183-188.
Amirzargar AA, Yalda A, Hajabolbaghi M, Khosravi F, Jabbari H. The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis. Int J Tuberc Lung Dis 2004; 8(8): 1017-1021.
Kim HS, Park MH, Song EY. Association of HLA-DR and HLA-DQ Genes With Susceptibility to Pulmonary Tuber-culosis in Koreans : Preliminary Evidence of Associations With Drug Resistance , Disease Severity , and Disease Recurrence. Hum Immunol 2005; 66(10): 1074-1081.
Dubaniewicz A. Frequency of DRB1 - DQB1 two-locus haplotypes in tuberculosis : Preliminary report. Tuberculosis 2005; 85(4): 259-267.
Lombard Z, Dalton DL, Venter PA, Williams RC, Bornman L. Association of HLA-DR, -DQ, and Vitamin D Receptor Alleles and Haplotypes with Tuberculosis in the Venda of South Africa. Hum Immunol 2006; 67(8): 643-654.
Selvaraj P, Raghavan S, Swaminathan S, Alagarasu K, Narendran G, Narayanan PR. HLA-DQB1 and -DPB1 allele profile in HIV infected patients with and without pulmonary tuberculosis of south India. Infect Genet Evol 2008; 8(5): 664-671.
XB, Li SZ, Jiang YJ. Correlation between polymorphisms of DRB1, -DQA1, and -DQB1 alleles and susceptibility to pulmonary tuberculosis in Tibetan population of China. J Third Mil Med Univ 2011; 33(2): 1254-1257.
Wu F, et al. NRAMP1, VDR, HLA-DRB1, and HLA-DQB1 gene polymorphisms in susceptibility to tuberculosis among the chinese kazakh population: A case-control study. Biomed Res Int 2013; 2013(1): 484535.
Kuranov AB, et al. HLA‐class II alleles in patients with drug‐resistant pulmonary tuberculosis in Kazakhstan. Tissue Antigens 2014; 83(2): 106-112.
Sang Tang NL, et al. Genetic susceptibility to Tuberculosis: Interaction between HLA-DQA1 and age of onset. Infect Genet Evol 2019; 68: 98-104.
Li C, Zhou Y, Xiang X, Zhou Y, He M. The Relationship of HLA-DQ Alleles with Tuberculosis Risk. Lung 2015; 193(4): 521-530.
Li D, et al. Polymorphism in the major histocompatibility complex (MHC class II B) genes of the Rufous-backed Bunting (Emberiza jankowskii). Peer J 2017; 2017(1): 1-23.
Jia Z, Gong W, Liang Y, Wu X, Zhao W. Prediction and analyses of HLA-II restricted Mycobacterium tuberculosis CD4+ T cell epitopes in the Chinese population. Biotechnol Appl Biochem 2022; 69(3): 1002-1014.
Harishankar M, Selvaraj P, Bethunaickan R. Influence of genetic polymorphism towards pulmonary tuberculosis susceptibility. Front Med 2018; 5: 1-18.
Ryan SO, Cobb BA. Roles for major histocompatibility complex glycosylation in immune function. Semin Immunopathol 2012; 34(3): 425-441.
Sarro S, et al. Differential HLA Allele Frequency in M. africanum vs. M. tuberculosis in Mali. HLA 2020; 93(1): 24-31.
Oliveira-Cortez A, Melo AC, Chaves VE, Condino-Neto A, Camargos P. Do HLA class II genes protect against pulmonary tuberculosis? A systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 2016; 35(10): 1567-1580.
Kuranov AB, Kozhamkulov UA, Vavilov MN, Belova ES, Bismilda VL, Alenova AH. HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan. Tissue Antigens 2014; 83(2): 106-112.
Chatterjee N, Ojha R, Khatoon N, Prajapati VK. Scrutinizing Mycobacterium tuberculosis membrane and secretory proteins to formulate multiepitope subunit vaccine against pulmonary tuberculosis by utilizing immunoinformatic approaches. Int J Biol Macromol 2018; 118: 180-188.
Das KK. an in Silico Study of the Genes Interaction and Association With Tuberculosis Disease. Int J Res Anal Rev 2022; 9(3): 789-798. [Online]. Available: www.ijrar.org
Dallmann-Sauer M, Correa-Macedo W, Schurr E. Human genetics of mycobacterial disease. Mamm Genome 2018; 29(7-8): 523-538.
Choshi P, et al. The association of class II HLA alleles with tuberculosis-associated immune reconstitution inflammatory syndrome. PLOS Pathog 2025; 21: 1-8.
Hosking L, et al. Detection of genotyping errors by Hardy - Weinberg equilibrium testing. Eur J Hum Genet 2004; 12(5): 395-399.
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Policy for Journals/Articles with Open Access
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work
Policy for Journals / Manuscript with Paid Access
Authors who publish with this journal agree to the following terms:
- Publisher retain copyright .
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work .